蜱唾液腺蛋白Salp20的补体抑制机制和卵黄发生的激素调控
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摘要
蜱类是世界广泛分布的专性吸血外寄生物，由其传播的人畜疾病非常多，对人类及畜牧业发展危害极大。肩突硬蜱（Ixodes scapularis），又名鹿蜱、黑腿壁虱，可传播多种病原体，包括莱姆病病原体伯格多弗疏螺旋体（Borrelia burgdorferi）。肩突硬蜱唾液腺分泌多种具有抗炎症反应、抗凝血和抗免疫反应的唾液分子到宿主体内，抑制宿主对蜱体表吸血的抵御反应。该蜱唾液腺蛋白Salp20能保护莱姆病血清敏感型病原体伽氏疏螺旋体（B. garinii）免受补体介导的裂解。
本文表达纯化了蜱唾液腺蛋白Salp20，对其分离纯化条件进行了优化，并对其补体抑制机制进行了研究。该研究对蜱媒疾病防治和畜牧业发展具有重要的理论和实际应用意义。
优化后的分离条件为：500ml样品量流经500μl的Ni-NTA亲和层析柱，用2ml含有20mM咪唑的缓冲液清洗四次，用250μl含有500mM咪唑的洗脱液洗脱四次并收集样品。SDS-PAGE和Western blot分析所得蛋白样品，结果显示蛋白具有高纯度且为目的蛋白Salp20。纯化的Salp20能够保护伽氏疏螺旋体免受补体裂解，证明分离纯化所得蛋白具有很高的生物学活性。
用C3b单克隆抗体检测莱姆病病原体表面C3b的沉积，免疫荧光分析结果显示血清敏感型病原体伽氏疏螺旋体表面有大量的C3b沉积，而血清抗型伯格多弗疏螺旋体表面C3b沉积量极少。说明血清敏感型病原体伽氏疏螺旋体能够引发强烈的补体反应，而血清抗型伯格多弗疏螺旋体不能。
用C3b和P因子单克隆抗体检测伽氏疏螺旋体表面补体替代途径中C3b和P因子的沉积，免疫荧光分析结果显示菌体表面有大量的C3b和P因子沉积，说明伽氏疏螺旋体引发了强烈的补体替代途径反应。向反应体系加入10μg/ml Salp20后，菌体表面没有C3b和P因子沉积，说明Salp20可抑制补体替代途径中的C3b和P因子结合到伽氏疏螺旋体表面。
伽氏疏螺旋体与10μg/ml P因子反应后，菌体表面无P因子的沉积。伽氏疏螺旋体与C3缺失型人血清反应后，发现菌体表面无P因子。表明P因子不能直接与伽氏疏螺旋体表面结合来起始补体替代途径。因此Salp20通过P因子结合，使其不能稳定C3转化酶，抑制了C3b蛋白的产生，从而抑制了补体替代途径。
研究了两种激素20-羟基蜕皮酮（20-hydroxyecdysone，20E）和保幼激素III（juvenile hormone III，JH III）对长角血蜱（Haemaphysalis longicornis）孤雌生殖种群卵黄发生的影响，对揭示蜱类生殖生物学规律和蜱类防治具有重要的科学意义。
蜱在宿主体表吸血3天后，向半饱血成蜱注射20E和JH III，20E的最大注射剂量为10μg/tick，JH III的最大注射剂量为5μg/tick。注射后三天检测结果。体式显微镜下观察20E注射剂量为0.5μg/tick和1μg/tick20E蜱的卵巢充满了含有卵黄颗粒的卵细胞，卵巢体积较大，整体呈现棕黄色，而注射对照组卵巢体积极小，呈白色半透明状。这两个注射剂量组蜱的卵巢重量占体重比例，脂肪体、血淋巴和卵巢中卵黄原蛋白白含量和卵黄原蛋白含量与对照组相比较显著增高。注射JH III蜱的的卵巢重量占体重比例，脂肪体、血淋巴和卵巢中卵黄原蛋白白含量和卵黄原蛋白含量与对照组相比较无显著差异。说明20E对半饱血期孤雌生殖长角血蜱卵黄发生和卵黄原蛋白的摄取具有促进作用，而JH III无作用。向饱血当天成蜱注射20E和JH III，20E的最大注射剂量为1μg/tick，JH III的最大注射剂量为0.5μg/g bw。注射后四天检测结果。结果显示20E和JH III注射组蜱卵巢重量，脂肪体、血淋巴、卵巢组织中卵黄原蛋白和Vn含量与对照组无显著差异。说明这两种激素对饱血期长角血蜱卵黄发生无作用。这些结果表明20E对半饱血蜱卵黄发生具有促进作用，但对饱血期蜱卵黄发生无显著作用。JH III对半饱血期和饱血期蜱的卵黄发生均无显著影响。
Ticks are widely distributed geographically and hematophagous arthropods and they areamong the most important vectors of human and animal diseases. Ixodes scapularis, theblacklegged tick, commonly known as a deer tick, can transmit multiple pathogens, includingBorrelia burgdorferi, the agent of Lyme disease. I. scapularis ticks secrete numerous salivaryanti-inflammatory, anti-hemostatic and immunosuppressive compounds into the host toinhibit host responses that could interfere with feeding on the surface of host. I. scapularissalivary protein20(Salp20) protects B. garinii，Lyme disease serum-sensitive pathogen,from complement mediated lysis.
In this study, tick salivary gland protein20(Salp20) was expressed and purified,extraction-purification condition was optimized and complement inhibition mechanism wasinvestigated. This research could be of important significance of theory and application inprevention and control of tick-borne diseases and development of animal husbandry.
Optimized extraction-purification condition:500ml sample was passed through500μlNi-NTA affinity column, column was washed by2ml wash buffer containing20mMimidazole four times, then eluted by250μl elution buffer containing500mM imidazole fourtimes and elutions were collected. SDS-PAGE and Western blot analysis showed that thepurity of Salp20was high and it was target protein Salp20. Purified Salp20protected B.garinii from complement lysis showing that biological activity of purified Salp20was veryhigh.
C3b deposition on the surface of Lyme disease pathogens were analyzed by detectingbound C3b monoclonal antibody. Immunofluorescence results showed large numbers ofcomponent C3b were deposited on the surface of B. garinii, almost no C3b was detected onthe surface of B. burgdorferi. The results suggested complement pathways were intensivelyactivated by sensitive B. garinii, but not B. burgdorferi.
The deposition on B. garinii surface of alternative pathway C3b and properdin wereanalyzed by detecting bound C3b and properdin monoclonal antibody. Immunofluorescenceresults showed large numbers of component C3b and properdin were deposited on the surfaceof B. garinii. The results suggested alternative complement pathways were intensivelyactivated by B. garinii. Neither C3b nor properdin was found on the bacteria surface afteradding10μg/ml Salp20to reaction system. These results suggested Salp20inhibited C3b andproperdin from binding to the surface of B. garinii.
No properdin deposition was found on the surface of B. garinii after reacting with10 μg/ml properdin. Also no properdin deposition was found on the surface of B. garinii afterreacting with C3depletion human serum. These results suggested it is impossible thatalternative complement pathway is initiated by direct binding of properdin. So Salp20inhibited the alternative complement pathway by preventing properdin from binding to C3convertase, accelerating the decay of the C3convertase and leading less C3b production.
It was also investigated that the20-hydroxyecdysone (20E) and juvenile hormone III (JHIII) regulation of vitellogenesis in parthenogenesis population of Haemaphysalis longicornis.This study could be of important scientific significance in revealing the reproductivebiological laws and prevention and control in ticks.
Partially fed adults ticks were injected with20E (up to10μg/tick) and JH III（up to5μg/tick）while they were attached and feeding on the host for3days. Ticks on-host wereexamined3days after injection. Ovaries (20E;0.5,1μg/tick) were covered with oocytesthose were large, yolk-filled and reddish-brown by observing with a stereoscopic microscope.However, ovary of vehicle-injected tick was very thin and translucent white in hue. The fatbody vitelligenin (Vg) content, hemolymph Vg concentration and ovary vitellin (Vn) contentof ticks injected with0.5and1μg/tick20E were significantly higher than vehicle-injectedcontrols. Ticks injected with JH III were not statistically different from vehicle-injected ticks.These results showed that20E, not JH III，stimulated both vitellogenesis and Vg uptake intooocytes in partially fed ticks. Engorged ticks were also injected with20E (up to1μg/g bw)and JH III (up to0.5μg/g bw). Ticks were examined4days after injection. Engorged ticksinjected with20E and JH III showed no significant differences from untreated ticks in eitherovary weight or concentration of fat body Vg, hemolymph Vg and ovarian Vn. These resultsdemonstrate that20E, and not JH III, stimulated vitellogenesis in partially fed ticks whileneither20E nor JH III had significant effects on vitellogenesis of engorged ticks.
本文表达纯化了蜱唾液腺蛋白Salp20，对其分离纯化条件进行了优化，并对其补体抑制机制进行了研究。该研究对蜱媒疾病防治和畜牧业发展具有重要的理论和实际应用意义。
优化后的分离条件为：500ml样品量流经500μl的Ni-NTA亲和层析柱，用2ml含有20mM咪唑的缓冲液清洗四次，用250μl含有500mM咪唑的洗脱液洗脱四次并收集样品。SDS-PAGE和Western blot分析所得蛋白样品，结果显示蛋白具有高纯度且为目的蛋白Salp20。纯化的Salp20能够保护伽氏疏螺旋体免受补体裂解，证明分离纯化所得蛋白具有很高的生物学活性。
用C3b单克隆抗体检测莱姆病病原体表面C3b的沉积，免疫荧光分析结果显示血清敏感型病原体伽氏疏螺旋体表面有大量的C3b沉积，而血清抗型伯格多弗疏螺旋体表面C3b沉积量极少。说明血清敏感型病原体伽氏疏螺旋体能够引发强烈的补体反应，而血清抗型伯格多弗疏螺旋体不能。
用C3b和P因子单克隆抗体检测伽氏疏螺旋体表面补体替代途径中C3b和P因子的沉积，免疫荧光分析结果显示菌体表面有大量的C3b和P因子沉积，说明伽氏疏螺旋体引发了强烈的补体替代途径反应。向反应体系加入10μg/ml Salp20后，菌体表面没有C3b和P因子沉积，说明Salp20可抑制补体替代途径中的C3b和P因子结合到伽氏疏螺旋体表面。
伽氏疏螺旋体与10μg/ml P因子反应后，菌体表面无P因子的沉积。伽氏疏螺旋体与C3缺失型人血清反应后，发现菌体表面无P因子。表明P因子不能直接与伽氏疏螺旋体表面结合来起始补体替代途径。因此Salp20通过P因子结合，使其不能稳定C3转化酶，抑制了C3b蛋白的产生，从而抑制了补体替代途径。
研究了两种激素20-羟基蜕皮酮（20-hydroxyecdysone，20E）和保幼激素III（juvenile hormone III，JH III）对长角血蜱（Haemaphysalis longicornis）孤雌生殖种群卵黄发生的影响，对揭示蜱类生殖生物学规律和蜱类防治具有重要的科学意义。
蜱在宿主体表吸血3天后，向半饱血成蜱注射20E和JH III，20E的最大注射剂量为10μg/tick，JH III的最大注射剂量为5μg/tick。注射后三天检测结果。体式显微镜下观察20E注射剂量为0.5μg/tick和1μg/tick20E蜱的卵巢充满了含有卵黄颗粒的卵细胞，卵巢体积较大，整体呈现棕黄色，而注射对照组卵巢体积极小，呈白色半透明状。这两个注射剂量组蜱的卵巢重量占体重比例，脂肪体、血淋巴和卵巢中卵黄原蛋白白含量和卵黄原蛋白含量与对照组相比较显著增高。注射JH III蜱的的卵巢重量占体重比例，脂肪体、血淋巴和卵巢中卵黄原蛋白白含量和卵黄原蛋白含量与对照组相比较无显著差异。说明20E对半饱血期孤雌生殖长角血蜱卵黄发生和卵黄原蛋白的摄取具有促进作用，而JH III无作用。向饱血当天成蜱注射20E和JH III，20E的最大注射剂量为1μg/tick，JH III的最大注射剂量为0.5μg/g bw。注射后四天检测结果。结果显示20E和JH III注射组蜱卵巢重量，脂肪体、血淋巴、卵巢组织中卵黄原蛋白和Vn含量与对照组无显著差异。说明这两种激素对饱血期长角血蜱卵黄发生无作用。这些结果表明20E对半饱血蜱卵黄发生具有促进作用，但对饱血期蜱卵黄发生无显著作用。JH III对半饱血期和饱血期蜱的卵黄发生均无显著影响。
Ticks are widely distributed geographically and hematophagous arthropods and they areamong the most important vectors of human and animal diseases. Ixodes scapularis, theblacklegged tick, commonly known as a deer tick, can transmit multiple pathogens, includingBorrelia burgdorferi, the agent of Lyme disease. I. scapularis ticks secrete numerous salivaryanti-inflammatory, anti-hemostatic and immunosuppressive compounds into the host toinhibit host responses that could interfere with feeding on the surface of host. I. scapularissalivary protein20(Salp20) protects B. garinii，Lyme disease serum-sensitive pathogen,from complement mediated lysis.
In this study, tick salivary gland protein20(Salp20) was expressed and purified,extraction-purification condition was optimized and complement inhibition mechanism wasinvestigated. This research could be of important significance of theory and application inprevention and control of tick-borne diseases and development of animal husbandry.
Optimized extraction-purification condition:500ml sample was passed through500μlNi-NTA affinity column, column was washed by2ml wash buffer containing20mMimidazole four times, then eluted by250μl elution buffer containing500mM imidazole fourtimes and elutions were collected. SDS-PAGE and Western blot analysis showed that thepurity of Salp20was high and it was target protein Salp20. Purified Salp20protected B.garinii from complement lysis showing that biological activity of purified Salp20was veryhigh.
C3b deposition on the surface of Lyme disease pathogens were analyzed by detectingbound C3b monoclonal antibody. Immunofluorescence results showed large numbers ofcomponent C3b were deposited on the surface of B. garinii, almost no C3b was detected onthe surface of B. burgdorferi. The results suggested complement pathways were intensivelyactivated by sensitive B. garinii, but not B. burgdorferi.
The deposition on B. garinii surface of alternative pathway C3b and properdin wereanalyzed by detecting bound C3b and properdin monoclonal antibody. Immunofluorescenceresults showed large numbers of component C3b and properdin were deposited on the surfaceof B. garinii. The results suggested alternative complement pathways were intensivelyactivated by B. garinii. Neither C3b nor properdin was found on the bacteria surface afteradding10μg/ml Salp20to reaction system. These results suggested Salp20inhibited C3b andproperdin from binding to the surface of B. garinii.
No properdin deposition was found on the surface of B. garinii after reacting with10 μg/ml properdin. Also no properdin deposition was found on the surface of B. garinii afterreacting with C3depletion human serum. These results suggested it is impossible thatalternative complement pathway is initiated by direct binding of properdin. So Salp20inhibited the alternative complement pathway by preventing properdin from binding to C3convertase, accelerating the decay of the C3convertase and leading less C3b production.
It was also investigated that the20-hydroxyecdysone (20E) and juvenile hormone III (JHIII) regulation of vitellogenesis in parthenogenesis population of Haemaphysalis longicornis.This study could be of important scientific significance in revealing the reproductivebiological laws and prevention and control in ticks.
Partially fed adults ticks were injected with20E (up to10μg/tick) and JH III（up to5μg/tick）while they were attached and feeding on the host for3days. Ticks on-host wereexamined3days after injection. Ovaries (20E;0.5,1μg/tick) were covered with oocytesthose were large, yolk-filled and reddish-brown by observing with a stereoscopic microscope.However, ovary of vehicle-injected tick was very thin and translucent white in hue. The fatbody vitelligenin (Vg) content, hemolymph Vg concentration and ovary vitellin (Vn) contentof ticks injected with0.5and1μg/tick20E were significantly higher than vehicle-injectedcontrols. Ticks injected with JH III were not statistically different from vehicle-injected ticks.These results showed that20E, not JH III，stimulated both vitellogenesis and Vg uptake intooocytes in partially fed ticks. Engorged ticks were also injected with20E (up to1μg/g bw)and JH III (up to0.5μg/g bw). Ticks were examined4days after injection. Engorged ticksinjected with20E and JH III showed no significant differences from untreated ticks in eitherovary weight or concentration of fat body Vg, hemolymph Vg and ovarian Vn. These resultsdemonstrate that20E, and not JH III, stimulated vitellogenesis in partially fed ticks whileneither20E nor JH III had significant effects on vitellogenesis of engorged ticks.
引文
Abbas A. K, A. H. Lichtman, and S. Pillai.2010. Cellular and Molecular Immunology.(6thed.). Elsevier.
Abbas, A. K., A. H. Lichtman, and J. S. Pober.2000. Cellular and Molecular Immunology.(4th ed.). W.B. Saunders Company, Philadelphia, PA.
Alarcon-Chaidez, F. J., U. U. Muller-Doblies, and S. Wikel.2003. Characterization of arecombinant immunomodulatory protein from the salivary glands of Dermacentorandersoni. Parasite Immunol.25:69-77.
Aljamali, M., A. S. Bowman, J. W. Dillwith, J. S. Tucker, G. W. Yates, R. C. Essenberg, andJ. R. Sauer.2002. Identity and synthesis of prostaglandins in the lone star tick,Amblyomma americanum, as assessed by radio-immunoassay and gaschromatography/mass spectrometry. Insect Biochem Mol Biol.32:331-341.
Anastopoulos, P., M. J. Thurn, and K. W. Broady.1991. Anticoagulant in the tick Ixodesholocyclus. Aust Vet J.68:366-367.
Anderson, J. F.2002. The natural history of ticks. Med Clin North Am.86:205-218.
Andrade, B. B., C. R. Teixeira, A. Barral, and M. Barral-Netto.2005. Haematophagousarthropod saliva and host defense system: a tale of tear and blood. An Acad Bras Cienc.77:665-693.
Anguita, J., N. Ramamoorthi, J. W. Hovius, S. Das, V. Thomas, R. Persinski, D. Conze, P. W.Askenase, M. Rincon, F. S. Kantor, and E. Fikrig.2002. Salp15, an Ixodes scapularissalivary protein, inhibits CD4+T cell activation. Immunity.16:849-859.
Baranton G., D. Postic, I. Saint Girons, P. Boerlin, JC. Piffaretti, M. Assous, and P. A.Grimont.1992. Delineation of Borrelia burgdorferi sensu stricto, Borrelia garinii sp.nov., and group VS461associated with lyme borreliosis. Int J Syst Bacteriol.42(3):378-383.
Bergman, D. K., M. J. Palmer, M. J. Caimano, J. D. Radolf, and S. K. Wikel.2000. Isolationand molecular cloning of a secreted immunosuppressant protein from Dermacentorandersoni salivary gland. J Parasitol.86:516-525.
Bergman, D. K., R. N. Ramachandra, and S. K. Wikel.1998. Characterization of animmunosuppressant protein from Dermacentor andersoni (Acari: Ixodidae) salivaryglands. J Med Entomol.35:505-509.
Bowman, A. S., J. R. Sauer, K. Zhu, and J. W. Dillwith.1995. Biosynthesis of salivaryprostaglandins in the lone star tick, Amblyomma americanum. Insect Biochem Mol Biol.25:735-741.
Bowman, A. S., J. W. Dillwith, and J. R. Sauer.1996. Tick salivary prostaglandins: Presence,origin and significance. Parasitol Today.12:388-396.
Breitner-Ruddock, S., R. Würzner J rg Schulze, and V. Brade.1997. Heterogeneity in thecomplement-dependent bacteriolysis within the species of Borrelia burgdorferi. MedMicrobiol Immunol.185:253-260.
Brossard, M., and S. K. Wikel.2004. Tick immunobiology. Parasitol.129Suppl: S161-176.
Burgdorfer W, A. G. Barbour, S. F. Hayes, J. L. Benach, E. Grunwaldt, and J. P. Davis.1982.Lyme disease-a tick-borne spirochetosis? Science.216(4552):1317-9.
Cavassani, K. A., J. C. Aliberti, A. R. Dias, J. S. Silva, and B. R. Ferreira.2005. Tick salivainhibits differentiation, maturation and function of murine bone-marrow-deriveddendritic cells. Immunology.114:235-245.
Champagne, D. E.2004. Antihemostatic strategies of blood-feeding arthropods. Curr DrugTargets Cardiovasc Haematol Disord.4:375-396.
Champagne, D. E.2005. Antihemostatic molecules from saliva of blood-feeding arthropods.Pathophysiol Haemost Thromb.34:221-227.
Chinery, W. A., and E. Ayitey-Smith.1977. Histamine blocking agent in the salivary glandhomogenate of the tick Rhipicephalus sanguineus sanguineus. Nature.265:366-367.
Chinzei, Y., and D. Taylor.1994. Hormonal regulation of vitellogenin biosynthesis in ticks.In: Harris KF ed. Advances in Disease Vector Research. Vol.10. Springer-Verlag, NewYork. pp.1-22.
Ciprandi, A., S. K. de Oliveira, A. Masuda, F. Horn, and C. Termignoni.2006. Boophilusmicroplus: its saliva contains microphilin, a small thrombin inhibitor. Exp Parasitol.114:40-46.
Connat, J. L., J. Ducommun, and P. A. Diehl.1983. Juvenile hormone-like substances caninduce vitellogenesis in the tick Ornithodoros moubata (Acarina: Argasidae).International Journal of Invertebrate Reproduction.6:285-294.
Daix, V., H. Schroeder, N. Praet, J. P. Georgin, I. Chiappino, L. Gillet, K. de Fays, Y.Decrem, G. Leboulle, E. Godfroid, A. Bollen, P. P. Pastoret, L. Gern, P. M. Sharp, andA. Vanderplasschen.2007. Ixodes ticks belonging to the Ixodes ricinus complex encodea family of anticomplement proteins. Insect Mol Biol.16:155-166.
Das, S., G. Banerjee, K. DePonte, N. Marcantonio, F. S. Kantor, and E. Fikrig.2001.Salp25D, an Ixodes scapularis antioxidant, is1of14immunodominant antigens inengorged tick salivary glands. J Infect Dis.184:1056-1064.
de Silva A. M., K.R. Tyson, and U. Pal.2009. Molecular characterization of the tick–Borreliainterface. Front Biosci.14:3051-3063.
Dees, W. H., D. E. Sonenshine, and E. Breidling.1984. Ecdysteroids in the American dogtick, Dermacentor variabilis (Acari: Ixodidae), during different periods of tickdevelopment. J Med Entomol.21(5):514-523.
Dennis, D. T., and J. F. Piesman.2005. Overview of tick-borne infections of humans. In Tick-Borne Diseases of Humans. J. L. Goodman, D. T. Dennis, and D. E. Sonenshine. Editors.American Society for Microbiology Press. Washingtion, D.C. pp.3-11.
Dickinson, R. G., J. E. O'Hagan, M. Schotz, K. C. Binnington, and M. P. Hegarty.1976.Prostaglandin in the saliva of the cattle tick Boophilus microplus. Aust J Exp Biol MedSci.54:475-486.
邓国藩，姜在阶.1991.中国经济昆虫志.第三十九册，蜱螨亚纲硬蜱科.北京：科学出版社.18-19.
Edwards, M. S., D. L. Kasper, H. J. Jennings, C. J. Baker, and A. Nicholson-Weller.1982.Capsular sialic acid prevents activation of the alternative complement pathway by typeIII, group B streptococci. J Immunol128:1278-1283.
Ehebauer, M. T., B. J. Mans, A. R. Gaspar, and A. W. Neitz.2002. Identification of extrinsicblood coagulation pathway inhibitors from the tick Ornithodoros savignyi (Acari:Argasidae). Exp Parasitol.101:138-148.
Fearon, D. T.1979. Regulation of the amplification C3convertase of human complement byan inhibitory protein isolated from human erythrocyte membrane. Proc Natl Acad Sci US A.76:5867-5871.
Fearon, D. T. and K. F. Austen.1975. Properdin: binding to C3b and stabilization of the C3b-dependent C3convertase. J Exp Med.142:856-863.
Ferreira, B. R. and J. S. Silva.1998. Saliva of Rhipicephalus sanguineus tick impairs T cellproliferation and IFN-gamma-induced macrophage microbicidal activity. Vet ImmunolImmunopathol.64:279-293.
Ferreira, B. R. and J. S. Silva.1999. Successive tick infestations selectively promote a T-helper2cytokine profile in mice. Immunology.96:434-439.
Ferreira, C. A., I. Da Silva Vaz, S. S. da Silva, K. L. Haag, J. G. Valenzuela, and A. Masuda.2002. Cloning and partial characterization of a Boophilus microplus (Acari: Ixodidae)calreticulin. Exp Parasitol.101:25-34.
Fine, D. P., S. R. Marney, Jr., D. G. Colley, J. S. Sergent, and R. M. Des Prez.1972. C3shuntactivation in human serum chelated with EGTA. J Immunol.109:807-809.
Forsgren, A., R. H. Mclean, A. F. Michael, and P. G. Quie.1975. Studies of the alternatepathway in chelated serum. J Lab Clin Med.85(6):904-912.
Francischetti, I. M., J. G. Valenzuela, J. F. Andersen, T. N. Mather, and J. M. Ribeiro.2002.Ixolaris, a novel recombinant tissue factor pathway inhibitor (TFPI) from the salivarygland of the tick, Ixodes scapularis: identification of factor X and factor Xa as scaffoldsfor the inhibition of factor VIIa/tissue factor complex. Blood.99:3602-3612.
Francischetti, I. M., T. N. Mather, and J. M. Ribeiro.2004. Penthalaris, a novel recombinantfive-Kunitz tissue factor pathway inhibitor (TFPI) from the salivary gland of the tickvector of Lyme disease, Ixodes scapularis. Thromb Haemost.91:886-898.
Frauenschuh, A., C. A. Power, M. Deruaz, B. R. Ferreira, J. S. Silva, M. M. Teixeira, J. M.Dias, T. Martin, T. N. Wells, and A. E. Proudfoot.2007. Molecular cloning andcharacterization of a highly selective chemokine-binding protein from the tickRhipicephalus sanguineus. J Biol Chem.282:27250-27258.
Friesen, K. J., and W. R. Kaufman.2002. Quantification of vitellogenesis and its control by20-hydroxyecdysone in the ixodid tick, Amblyomma hebraeum. J Insect Physiol.48(8):773-782.
Friesen, K. J., and W. R. Kaufman.2004. Effects of20-hydroxyecdysone and other hormoneson egg development, and identification of a vitellin-binding protein in the ovary of thetick, Amblyomma hebraeum. J Insect Physiol.50(6):519-529.
Fujita, T., T. Inoue, K. Ogawa, K. Iida, and N. Tamura.1987. The mechanism of action ofdecay-accelerating factor (DAF). DAF inhibits the assembly of C3convertases bydissociating C2a and Bb. J Exp Med.166:1221-1228.
Ganapamo, F., B. Rutti, and M. Brossard.1995. In vitro production of interleukin-4andinterferon-gamma by lymph node cells from BALB/c mice infested with nymphal Ixodesricinus ticks. Immunology.85:120-124.
Gao, J., J. Luo, R. Fan, V. Fingerle, G. Guan, Z. Liu, Y. Li, H. Zhao, M. Ma, J. Liu, A. Liu,Q. Ren, Z. Dang, C. Sugimoto, and H. Yin.2007. Cloning and characterization of acDNA clone encoding calreticulin from Haemaphysalis qinghaiensis (Acari: Ixodidae).Parasitol Res.102:737-746.
Garg, R., I. J. Juncadella, N. Ramamoorthi, Ashish, S. K. Ananthanarayanan, V. Thomas, M.Rincon, J. K. Krueger, E. Fikrig, C. M. Yengo, and J. Anguita.2006. Cutting edge: CD4is the receptor for the tick saliva immunosuppressor, Salp15. J Immunol.177:6579-6583.
Gaspar, A. R., A. M. Joubert, J. C. Crause, and A. W. Neitz.1996. Isolation andcharacterization of an anticoagulant from the salivary glands of the tick, Ornithodorossavignyi (Acari: Argasidae). Exp Appl Acarol.20:583-598.
Gillespie, R. D., M. L. Mbow, and R. G. Titus.2000. The immunomodulatory factors ofbloodfeeding arthropod saliva. Parasite Immunol.22:319-331.
Goddard, J.1993. Physician's Guide to Arthropods of Medical Importance. CRC Press, BocaRaton, FL.
Gordon, J. R. and J. R. Allen.1991. Factors V and VII anticoagulant activities in the salivaryglands of feeding Dermacentor andersoni ticks. J Parasitol.77:167-170.
Gwakisa, P., K. Yoshihara, T. Long To, H. Gotoh, F. Amano, and E. Momotani.2001.Salivary gland extract of Rhipicephalus appendiculatus ticks inhibits in vitrotranscription and secretion of cytokines and production of nitric oxide by LPS-stimulatedJA-4cells. Vet Parasitol.99:53-61.
Hajnicka, V., I. Vancova, P. Kocakova, M. Slovak, J. Gasperik, M. Slavikova, R. S. Hails, M.Labuda, and P. A. Nuttall.2005. Manipulation of host cytokine network by ticks: apotential gateway for pathogen transmission. Parasitology.130:333-342.
Hajnicka, V., P. Kocakova, M. Slavikova, M. Slovak, J. Gasperik, N. Fuchsberger, and P. A.Nuttall.2001. Anti-interleukin-8activity of tick salivary gland extracts. ParasiteImmunol.23:483-489.
Hannier, S., J. Liversidge, J. M. Sternberg, and A. S. Bowman.2004. Characterization of theB-cell inhibitory protein factor in Ixodes ricinus tick saliva: a potential role in enhancedBorrelia burgdorferi transmission. Immunology.113:401-408.
Harris, C. L., D. M. Pettigrew, S. M. Lea, and B. P. Morgan.2007. Decay-accelerating factormust bind both components of the complement alternative pathway C3convertase tomediate efficient decay. J Immunol.178:352-359.
Hiemstra, P. S., A. Gorter, M. E. Stuurman, L. A. Van Es, M. R. Daha.2005. Activation ofthe alternative pathway of complement by human serum IgA. Eur J Immunol.17(3):321-326.
Hoffmann, A., P. Walsmann, G. Riesener, M. Paintz, and F. Markwardt.1991. Isolation andcharacterization of a thrombin inhibitor from the tick Ixodes ricinus. Pharmazie.46:209-212.
Horn, F., P. C. dos Santos, and C. Termignoni.2000. Boophilus microplus anticoagulantprotein: an antithrombin inhibitor isolated from the cattle tick saliva. Arch BiochemBiophys.384:68-73.
Hourcade, D. E.2006. The role of properdin in the assembly of the alternative pathway C3convertases of complement. J Biol Chem.281:2128-32.
Hourcade, D. E., L. M. Mitchell, and M. E. Medof.1999. Decay acceleration of thecomplement alternative pathway C3convertase. Immunopharmacology.42:167-173.
Hovius, J. W., N. Ramamoorthi, C. Van't Veer, K. A. de Groot, A. M. Nijhof, F. Jongejan, A.P. van Dam, and E. Fikrig.2007. Identification of Salp15homologues in Ixodes ricinusticks. Vector Borne Zoonotic Dis.7:296-303.
Ibrahim, M. A., A. H. Ghazy, T. M. Maharem, and M. I. Khalil.2001. Factor Xa (FXa)inhibitor from the nymphs of the camel tick Hyalomma dromedarii. Comp BiochemPhysiol B Biochem Mol Biol.130:501-512.
Ibrahim, M. A., A. H. Ghazy, T. Maharem, and M. Khalil.2001. Isolation and properties oftwo forms of thrombin inhibitor from the nymphs of the camel tick Hyalommadromedarii (Acari: Ixodidae). Exp Appl Acarol.25:675-698.
Inokuma, H., D. H. Kemp, and P. Willadsen.1994. Comparison of prostaglandin E2(PGE2)in salivary gland of Boophilus microplus, Haemaphysalis longicornis and Ixodesholocyclus, and quantification of PGE2in saliva, hemolymph, ovary and gut of B.microplus. J Vet Med Sci.56:1217-1218.
Inokuma, H., T. Aita, K. Tamura, and T. Onishi.1997. Effect of infestation withRhipicephalus sanguineus on the antibody productivity in dogs. Med Vet Entomol.11:201-202.
Iwanaga, S., M. Okada, H. Isawa, A. Morita, M. Yuda, and Y. Chinzei.2003. Identificationand characterization of novel salivary thrombin inhibitors from the ixodidae tick,Haemaphysalis longicornis. Eur J Biochem.270:1926-1934.
James, A. M., X. X. Zhu, and J. H. Oliver Jr.1997. Vitellogenin and ecdysteroid titers inIxodes scapularis during vitellogenesis. J Parasitol.83(4):559-563.
Jaworski, D. C., F. A. Simmen, W. Lamoreaux, L. B. Coons, M. T. Muller, and G. RNeedham.1995. A secreted calreticulin protein in the ixodid tick (Amblyommaamericanum) saliva. J Insect Physiol.41:369-375.
Joubert, A. M., J. C. Crause, A. R. Gaspar, F. C. Clarke, A. M. Spickett, and A. W. Neitz.1995. Isolation and characterization of an anticoagulant present in the salivary glands ofthe bont-legged tick, Hyalomma truncatum. Exp Appl Acarol.19:79-92.
Juncadella, I. J., R. Garg, S. K. Ananthnarayanan, C. M. Yengo, and J. Anguita.2007. T-cellsignaling pathways inhibited by the tick saliva immunosuppressor, Salp15. FEMSImmunol Med Microbiol.49:433-438.
Kato, N., S. Iwanaga, T. Okayama, H. Isawa, M. Yuda, and Y. Chinzei.2005. Identificationand characterization of the plasma kallikrein-kinin system inhibitor, haemaphysalin,from hard tick, Haemaphysalis longicornis. Thromb Haemost.93:359-367.
Kaufman, W. R.1991. Correlation between haemolymph ecdysteroid titre, salivary glanddegeneration and ovarian development in the ixodid tick, Amblyomma hebraeum Koch.J Insect Physiol.37(2):95-99.
Kimura, Y., T. Miwa, L. Zhou, and W. C. Song.2008. Activator-specific requirement ofproperdin in the initiation and amplification of the alternative pathway complement.Blood.111:732-740.
Kirkitadze, M.D. and P. N. Barlow.2001. Structure and flexibility of the multiple domainproteins that regulate complement activation. Immunol Rev180:146-161.
Koh, C. Y., M. Kazimirova, A. Trimnell, P. Takac, M. Labuda, P. A. Nuttall, and R. M. Kini.2007. Variegin, a novel fast and tight binding thrombin inhibitor from the tropical bonttick. J Biol Chem.282:29101-29113.
Kopecky, J. and M. Kuthejlova.1998. Suppressive effect of Ixodes ricinus salivary glandextract on mechanisms of natural immunity in vitro. Parasite Immunol.20:169-174.
Kopecky, J., M. Kuthejlova, and J. Pechova.1999. Salivary gland extract from Ixodes ricinusticks inhibits production of interferon-gamma by the upregulation of interleukin-10.Parasite Immunol.21:351-356.
Kovar, L., J. Kopecky, and B. Rihova.2001. Salivary gland extract from Ixodes ricinus tickpolarizes the cytokine profile toward Th2and suppresses proliferation of T lymphocytesin human PBMC culture. J Parasitol.87:1342-1348.
Kubes, M., N. Fuchsberger, M. Labuda, E. Zuffova, and P. A. Nuttall.1994. Salivary glandextracts of partially fed Dermacentor reticulatus ticks decrease natural killer cell activityin vitro. Immunology.82:113-116.
Kubes, M., P. Kocakova, M. Slovak, M. Slavikova, N. Fuchsberger, and P. A. Nuttall.2002.Heterogeneity in the effect of different ixodid tick species on human natural killer cellactivity. Parasite Immunol.24:23-28.
Kurtenbach, K., S. De Michelis, S. Etti, S. M. Scha fer, H. S. Sewell, V. Brade, and PKraiczy.2002. Host association of Borrelia burgdorferi sensu lato—the key role of hostcomplement. Trends Microbiol.10:74–79.
Kuthejlova, M., J. Kopecky, G. Stepanova, and A. Macela.2001. Tick salivary gland extractinhibits killing of Borrelia afzelii spirochetes by mouse macrophages. Infect Immun.69:575-578.
Lawrie, C. H., R. B. Sim, and P. A. Nuttall.2005. Investigation of the mechanisms of anti-complement activity in Ixodes ricinus ticks. Mol Immunol.42:31-38.
Lawrie, C. H., S. E. Randolph, and P. A. Nuttall.1999. Ixodes ticks: serum species sensitivityof anticomplement activity. Exp Parasitol.93:207-214.
Leboulle, G., M. Crippa, Y. Decrem, N. Mejri, M. Brossard, A. Bollen, and E. Godfroid.2002. Characterization of a novel salivary immunosuppressive protein from Ixodesricinus ticks. J Biol Chem.277:10083-10089.
Limo, M. K., W. P. Voigt, A. G. Tumbo-Oeri, R. M. Njogu, and O. K. ole-MoiYoi.1991.Purification and characterization of an anticoagulant from the salivary glands of theixodid tick Rhipicephalus appendiculatus. Exp Parasitol.72:418-429.
梁茂茂.2011.蜱虫的危害及防治.吉林畜牧兽医.32(9):43-45.
李知新，刘光远，田占成，谢俊仁，王路，龚真莉，柴慧萍，孙晓林.2007.实验室条件下长角血蜱甘肃株孤雌生殖种群的生物学特性.中国兽医科学.37(4)：277-281.
Macaluso, K. R. and S. K. Wikel.2001. Dermacentor andersoni: effects of repeatedinfestations on lymphocyte proliferation, cytokine production, and adhesion-moleculeexpression by BALB/c mice. Ann Trop Med Parasitol.95:413-427.
Mans, B. J. and A. W. Neitz.2004. Adaptation of ticks to a blood-feeding environment:evolution from a functional perspective. Insect Biochem Mol Biol.34:1-17.
Mans, B. J., A. I. Louw, and A. W. Neitz.2002. Amino acid sequence and structure modelingof savignin, a thrombin inhibitor from the tick, Ornithodoros savignyi. Insect BiochemMol Biol.32:821-828.
Mans, B. J., A. R. Gaspar, A. I. Louw, and A. W. Neitz.1998. Apyrase activity and plateletaggregation inhibitors in the tick Ornithodoros savignyi (Acari: Argasidae). Exp ApplAcarol.22:353-366.
Mans, B. J., J. F. Andersen, T. G. Schwan, and J. M. Ribeiro.2008. Characterization of anti-hemostatic factors in the argasid, Argas monolakensis: Implications for the evolution ofblood-feeding in the soft tick family. Insect Biochem Mol Biol.38:22-41.
Maxwell, S. S., T. A. Stoklasek, Y. Dash, K. R. Macaluso, and S. K. Wikel.2005. Tickmodulation of the in-vitro expression of adhesion molecules by skin-derived endothelialcells. Ann Trop Med Parasitol.99:661-672.
Montgomery, R. R., D. Lusitani, A. De Boisfleury Chevance, and S. E. Malawista.2004. Ticksaliva reduces adherence and area of human neutrophils. Infect Immun.72:2989-2994.
Morgan, B. P., and C. L. Harris.1999. Complement regulatory proteins. Academic Press. SanDiego, CA.
Motoyashiki, T., A. T. Tu, D. A. Azimov, and K. Ibragim.2003. Isolation of anticoagulantfrom the venom of tick, Boophilus calcaratus, from Uzbekistan. Thromb Res.110:235-241.
Muller-Doblies, U. U. and S. K. Wikel.2005. The Human Reaction to Ticks, In Tick-BorneDiseases of Humans. J. L. Goodman, D. T. Dennis, and D. E. Sonenshine. Editors.American Society for Microbiology. Washington DC. pp.102-22.
Muller-Doblies, U. U., S. S. Maxwell, V. D. Boppana, M. A. Mihalyo, S. J. McSorley, A. T.Vella, A. J. Adler, and S. K. Wikel.2007. Feeding by the tick, Ixodes scapularis, causesCD4+T cells responding to cognate antigen to develop the capacity to express IL-4.Parasite Immunol.29:485-499.
Narasimhan, S., R. A. Koski, B. Beaulieu, J. F. Anderson, N. Ramamoorthi, F. Kantor, M.Cappello, and E. Fikrig.2002. A novel family of anticoagulants from the saliva of Ixodesscapularis. Insect Mol Biol.11:641-650.
Neeper, M. P., L. Waxman, D. E. Smith, C. A. Schulman, M. Sardana, R. W. Ellis, L. W.Schaffer, P. K. Siegl, and G. P. Vlasuk.1990. Characterization of recombinant tickanticoagulant peptide. A highly selective inhibitor of blood coagulation factor Xa. J BiolChem.265:17746-17752.
Nicholson-Weller, A., J. Burge, D. T. Fearon, P. F. Weller, and K. F. Austen.1982. Isolationof a human erythrocyte membrane glycoprotein with decay-accelerating activity for C3convertases of the complement system. J Immunol.129:184-189.
Nienaber, J., A. R. Gaspar, and A. W. Neitz.1999. Savignin, a potent thrombin inhibitorisolated from the salivary glands of the tick Ornithodoros savignyi (Acari: Argasidae).Exp Parasitol.93:82-91.
Nunn, M. A., A. Sharma, G. C. Paesen, S. Adamson, O. Lissina, A. C. Willis, and P. A.Nuttall.2005. Complement inhibitor of C5activation from the soft tick Ornithodorosmoubata. J Immunol.174:2084-2091.
Nuttall, P. A., G. C. Paesen, C. H. Lawrie, and H. Wang.2000. Vector-host interactions indisease transmission. J Mol Microbiol Biotechnol.2:381-6.
Oliveira, C. J., K. A. Cavassani, D. D. More, G. P. Garlet, J. C. Aliberti, J. S. Silva, and B. R.Ferreira.2007. Tick saliva inhibits the chemotactic function of MIP-1alpha andselectively impairs chemotaxis of immature dendritic cells by down-regulating cell-surface CCR5. Int J Parasitol.38:705–716.
Paesen, G. C., P. L. Adams, K. Harlos, P. A. Nuttall, and D. I. Stuart.1999. Tick histamine-binding proteins: isolation, cloning, and three-dimensional structure. Mol Cell.3:661-671.
Pangburn, M. K.1986. Differences between the binding sites of the complement regulatoryproteins DAF, CR1, and factor H on C3convertases. J Immunol.136(6):2216-2221.
Pangburn, M. K. and H. J. Muller-Eberhard.1986. The C3convertase of the alternativepathway of human complement. Enzymic properties of the bimolecular proteinase.Biochem J.235:723-730.
Pechova, J., J. Kopecky, and J. Salat.2004. Effect of tick salivary gland extract on thecytokine production by mouse epidermal cells. Folia Parasitol (Praha).51:367-372.
Pillemer, L., L. Blum., I. H. Lepow, O. A. Ross, E. W. Todd, and A. C. Wardlaw.1954. Theproperdin system and immunity. I. Demonstration and isolation of a new serum protein,properdin, and its role in immune phenomena. Science.120:279-285.
Ramachandra, R. N. and S. K. Wikel.1992. Modulation of host-immune responses by ticks(Acari: Ixodidae): effect of salivary gland extracts on host macrophages and lymphocytecytokine production. J Med Entomol.29:818-826.
Ramachandra, R. N. and S. K. Wikel.1995. Effects of Dermacentor andersoni (Acari:Ixodidae) salivary gland extracts on Bos indicus and B. taurus lymphocytes andmacrophages: in vitro cytokine elaboration and lymphocyte blastogenesis. J MedEntomol.32:338-345.
Ribeiro, J. M.1987. Ixodes dammini: salivary anti-complement activity. Exp Parasitol.64:347-353.
Ribeiro, J. M. and I. M. Francischetti.2003. Role of arthropod saliva in blood feeding:sialome and post-sialome perspectives. Annu Rev Entomol.48:73-88.
Ribeiro, J. M. and T. N. Mather.1998. Ixodes scapularis: salivary kininase activity is ametallo dipeptidyl carboxypeptidase. Exp Parasitol.89:213-221.
Ribeiro, J. M., F. Alarcon-Chaidez, I. M. Francischetti, B. J. Mans, T. N. Mather, J. G.Valenzuela, and S. K. Wikel.2006. An annotated catalog of salivary gland transcriptsfrom Ixodes scapularis ticks. Insect Biochem Mol Biol.36:111-129.
Ribeiro, J. M., G. T. Makoul, and D. R. Robinson.1988. Ixodes dammini: evidence forsalivary prostacyclin secretion. J Parasitol.74:1068-1069.
Ribeiro, J. M., G. T. Makoul, J. Levine, D. R. Robinson, and A. Spielman.1985.Antihemostatic, antiinflammatory, and immunosuppressive properties of the saliva of atick, Ixodes dammini. J Exp Med.161:332-344.
Ribeiro, J. M., J. J. Weis, and S. R. Telford,3rd.1990. Saliva of the tick Ixodes damminiinhibits neutrophil function. Exp Parasitol.70:382-388.
Ribeiro, J. M., P. M. Evans, J. L. MacSwain, and J. Sauer.1992. Amblyomma americanum:characterization of salivary prostaglandins E2and F2alpha by RP-HPLC/bioassay andgas chromatography-mass spectrometry. Exp Parasitol.74:112-116.
Ribeiro, J. M., T. M. Endris, and R. Endris.1991. Saliva of the soft tick, Ornithodorosmoubata, contains anti-platelet and apyrase activities. Comp Biochem Physiol A.100:109-112.
Rosell-Davis, R., and L. B. Coons.1991. Determination of vitellogenin titer in thehemolymph of Dermacentor variabilis (Acarina: Ixodidae) using an indirect enzyme-linked immunosorbent assay. J Med Entomol.28(1):41-44.
Ross, G. D., J. D. Lambris, J. A. Cain, and S. L. Newman.1982. Generation of three differentfragments of bound C3with purified factor I or serum. I. Requirements for factor H vsCR1cofactor activity. J Immunol.129:2051-2060.
Roversi, P., O. Lissina, S. Johnson, N. Ahmat, G. C. Paesen, K. Ploss, W. Boland, M. A.Nunn, and S. M. Lea.2007. The structure of OMCI, a novel lipocalin inhibitor of thecomplement system. J Mol Biol.369:784-793.
Sa-Nunes, A., A. Bafica, D. A. Lucas, T. P. Conrads, T. D. Veenstra, J. F. Andersen, T. N.Mather, J. M. Ribeiro, and I. M. Francischetti.2007. Prostaglandin E2is a majorinhibitor of dendritic cell maturation and function in Ixodes scapularis saliva. JImmunol.179:1497-1505.
Sanders, M. L., D. C. Jaworski, J. L. Sanchez, R. F. DeFraites, G. E. Glass, A. L. Scott, S.Raha, B. C. Ritchie, G. R. Needham, and B. S. Schwartz.1998. Antibody to a cDNA-derived calreticulin protein from Amblyomma americanum as a biomarker of tickexposure in humans. Am J Trop Med Hyg.59:279-285.
Schoeler, G. B. and S. K. Wikel.2001. Modulation of host immunity by haematophagousarthropods. Ann Trop Med Parasitol.95:755-771.
Schoeler, G. B., S. A. Manweiler, and S. K. Wikel.1999. Ixodes scapularis: effects ofrepeated infestations with pathogen-free nymphs on macrophage and T lymphocytecytokine responses of BALB/c and C3H/HeN mice. Exp Parasitol.92:239-248.
Schoeler, G. B., S. A. Manweiler, and S. K. Wikel.2000. Cytokine responses of C3H/HeNmice infested with Ixodes scapularis or Ixodes pacificus nymphs. Parasite Immunol.22:31-40.
Schuijt, T. J., J. Coumou, S. Narasimhan, J. Dai, K. DePonte, D. Wouters, M. Brouwer, A.Oei, J. J.T.H. Roelofs, A. P. van Dam, T. van der Poll, C. van't Veer, J. W. Hovius, andE. Fikrig.2011. A Tick mannose-binding lectin inhibitor interferes with the vertebratecomplement cascade to enhance transmission of the Lyme disease agent. Cell HostMicrobe.10:136-146.
Schwaeble, W., H. P. Huemer, J. M st, M. P. Dierich, M. Str bel, C. Claus, K. B. Reid, andH. W. Ziegler-Heitbrock.1994. Expression of properdin in human monocytes. Eur JBiochem.219:759-764.
Schwaeble, W., W. Schwaeble, W. G. Dippold, M. K. Sch fer, H. Pohla, D. Jonas, Luttig B,Weihe E, H. P. Huemer, M. P. Dierich, and K. B. Reid.1993. Properdin, a positiveregulator of complement activation, is expressed in human T cell lines and peripheralblood T cells. J Immunol.151:2521-2528.
Seixas, A., K. J. Friesen, and W. R. Kaufman.2008. Effect of20-hydroxyecdysone andhaemolymph on oogenesis in the ixodid tick Amblyomma hebraeum. J Insect Physiol.54:1175-1183.
Seya, T. and J. P. Atkinson.1989. Functional properties of membrane cofactor protein ofcomplement. Biochem J.264:581-588.
Seya, T., J. R. Turner, and J. P. Atkinson.1986. Purification and characterization of amembrane protein (gp45-70) that is a cofactor for cleavage of C3b and C4b. J Exp Med.163:837-855.
Soares, C. A., C. M. Lima, M. C. Dolan, J. Piesman, C. B. Beard, and N. S. Zeidner.2005.Capillary feeding of specific dsRNA induces silencing of the isac gene in nymphalIxodes scapularis ticks. Insect Mol Biol.14:443-452.
Sonenshine, D. E.2005. The Biology of Tick Vectors of Human Disease, In Tick-BorneDiseases of Humans. J. L. Goodman, D. T. Dennis, and D. E. Sonenshine. Editors.American Society for Microbiology Press. Washington, DC. pp.12-35.
Sonenshine, D. E.,1991. Biology of Ticks. Oxford University Press. New York, NY.
Spitzer, D., L. M. Mitchell, J. P. Atkinson, and D. E. Hourcade.2007. Properdin can initiatecomplement activation by binding specific target surfaces and providing a platform forde novo convertase assembly. J Immunol.179:2600-2608.
Stover, C. M., J. C. Luckett, B. Echtenacher, A. Dupont, S. E. Figgitt, J. Brown, D. N.M nnel, and W. J. Schwaeble.2008. Properdin plays a protective role in polymicrobialseptic peritonitis. J Immunol.180:3313-3318.
Tanaka, A. S., R. Andreotti, A. Gomes, R. J. Torquato, M. U. Sampaio, and C. A. Sampaio.1999. A double headed serine proteinase inhibitor—human plasma kallikrein andelastase inhibitor—from Boophilus microplus larvae. Immunopharmacology.45:171-177.
Taylor D., A. Moribayashi, N. Agui, T. Shono, and Y. Chinzei.1997. Hormonal regulation ofvitellogenesis in the soft tick, Ornithodoros moubata. S. Kawashima and S. Kikuyama.Editors. Advances in Comparative Endocrinology. Monduzzi Editore. Bologna. Italy. pp.213-220.
Thompson D. M., S. M. S. Khalil, L. A. Jeffers, U. Ananthapadmanaban, D. E. Sonenshine,R. D. Mitchell, C. J. Osgood, C. S. Apperson, R. M. Roe.2005. In vivo role of20-hydroxyecdysone in the regulation of the vitellogenin mRNA and egg development inthe American dog tick, Dermacentor variabilis. J Insect Physiol.51(10):1105-1116.
Titus, R. G., J. V. Bishop, and J. S. Mejia.2006. The immunomodulatory factors of arthropodsaliva and the potential for these factors to serve as vaccine targets to prevent pathogentransmission. Parasite Immunol.28:131-141.
Tsuji, N., T. Kamio, T. Isobe, and K. Fujisaki.2001. Molecular characterization of aperoxiredoxin from the hard tick Haemaphysalis longicornis. Insect Mol Biol.10:121-129.
Tyson, K. R., C. Elkins, and A. M. de Silva.2008. A novel mechanism of complementinhibition unmasked by a tick salivary protein that binds to properdin. J Immunol.180:3964-3968.
Tyson, K., C. Elkins, H. Patterson, E. Fikrig and A. de Silva.2007. Biochemical andfunctional characterization of Salp20, an Ixodes scapularis complement pathway. InsectMol Biol.16(4):469-479.
Urioste, S., L. R. Hall, S. R. Telford,3rd, and R. G. Titus.1994. Saliva of the Lyme diseasevector, Ixodes dammini, blocks cell activation by a nonprostaglandin E2-dependentmechanism. J Exp Med.180:1077-1085.
Valenzuela, J. G.2004. Exploring tick saliva: from biochemistry to 'sialomes' and functionalgenomics. Parasitology.129Suppl: S83-94.
Valenzuela, J. G., I. M. Francischetti, V. M. Pham, M. K. Garfield, T. N. Mather, and J. M.Ribeiro.2002. Exploring the sialome of the tick Ixodes scapularis. J Exp Biol.205:2843-2864.
Valenzuela, J. G., R. Charlab, T. N. Mather, and J. M. Ribeiro.2000. Purification, cloning,and expression of a novel salivary anticomplement protein from the tick, Ixodesscapularis. J Biol Chem.275:18717-18723.
van Dam, A.P., A. Oei, R. Jaspars, C. Fijen, B. Wilske, L. Spanjaard, and J. Dankert.1997.Complement-mediated serum sensitivity among spiro-chetes that cause Lyme disease.Infect Immun.65:1228-1236.
van de Locht, A., M. T. Stubbs, W. Bode, T. Friedrich, C. Bollschweiler, W. Hoffken, and R.Huber.1996. The ornithodorin-thrombin crystal structure, a key to the TAP enigma?Embo J.15:6011-6017.
Vancova, I., M. Slovak, V. Hajnicka, M. Labuda, L. Simo, K. Peterkova, R. S. Hails, and P.A. Nuttall.2007. Differential anti-chemokine activity of Amblyomma variegatum adultticks during blood-feeding. Parasite Immunol.29:169-177.
Wang, H. and P. A. Nuttall.1994. Excretion of host immunoglobulin in tick saliva anddetection of IgG-binding proteins in tick haemolymph and salivary glands. Parasitology.109(4):525-530.
Wang, H. and P. A. Nuttall.1995. Immunoglobulin G binding proteins in male Rhipicephalusappendiculatus ticks. Parasite Immunol.17:517-524.
Wang, H., and P. A. Nuttall.1995. Immunoglobulin-G binding proteins in the ixodid ticks,Rhipicephalus appendiculatus, Amblyomma variegatum and Ixodes hexagonus.Parasitology.111(2):161-165.
Waxman, L., D. E. Smith, K. E. Arcuri, and G. P. Vlasuk.1990. Tick anticoagulant peptide(TAP) is a novel inhibitor of blood coagulation factor Xa. Science.248:593-596.
Weiler, J. M., M. R. Daha, K. F. Austen, and D. T. Fearon.1976. Control of the amplificationconvertase of complement by the plasma protein beta1H. Proc Natl Acad Sci U S A.73:3268-3272.
Whaley, K. and S. Ruddy.1976. Modulation of the alternative complement pathways by beta1H globulin. J Exp Med.144(5):1147-1163.
Wikel, S. K.1985. Effects of tick infestation on the plaque-forming cell response to a thymicdependent antigen. Ann Trop Med Parasitol.79:195-198.
Wikel, S. K.1996. Host immunity to ticks. Annu Rev Entomol.41:1-22.
Wikel, S. K.1999. Tick modulation of host immunity: an important factor in pathogentransmission. Int J Parasitol.29:851-9.
Xu, G., Q. Q. Fang, J. E. Keirans, and L. A. Durden.2004. Cloning and sequencing ofputative calreticulin complementary DNAs from four hard tick species. J Parasitol.90:73-78.
Yu, D., J. Liang, H. Yu, H. Wu, C. Xu, J. Liu, and R. Lai.2006. A tick B-cell inhibitoryprotein from salivary glands of the hard tick, Hyalomma asiaticum asiaticum. BiochemBiophys Res Commun.343:585-590.
Ze Chen, Xiaojun Yang, Fengju Bu, Xiaohong Yang, and Jingze Liu.2012. Morphological,biological and molecular characteristics of bisexual and parthenogenetic Haemaphysalislongicornis. Vet Parasitol.189(2012):344-352.
Zhu, K., A. S. Bowman, D. L. Brigham, R. C. Essenberg, J. W. Dillwith, and J. R. Sauer.1997. Isolation and characterization of americanin, a specific inhibitor of thrombin, fromthe salivary glands of the lone star tick Amblyomma americanum. Exp Parasitol.87:30-38.
Zhu, K., J. R. Sauer, A. S. Bowman, and J. W. Dillwith.1997. Identification andcharacterization of anticoagulant activities in the saliva of the lone star tick, Amblyommaamericanum. J Parasitol.83:38-43.
Zipfel, P. F., T. S. Jokiranta, J. Hellwage, V. Koistinen, and S. Meri.1999. The factor Hprotein family. Immunopharmacology.42:53-60.
周金林，周勇志，龚海燕，陈灵芝，曹杰.2004.我国长角血蜱孤雌生殖种群的发现和生物学特性的研究.中国媒介生物学及控制杂志.15(003)：173-174.
Abbas, A. K., A. H. Lichtman, and J. S. Pober.2000. Cellular and Molecular Immunology.(4th ed.). W.B. Saunders Company, Philadelphia, PA.
Alarcon-Chaidez, F. J., U. U. Muller-Doblies, and S. Wikel.2003. Characterization of arecombinant immunomodulatory protein from the salivary glands of Dermacentorandersoni. Parasite Immunol.25:69-77.
Aljamali, M., A. S. Bowman, J. W. Dillwith, J. S. Tucker, G. W. Yates, R. C. Essenberg, andJ. R. Sauer.2002. Identity and synthesis of prostaglandins in the lone star tick,Amblyomma americanum, as assessed by radio-immunoassay and gaschromatography/mass spectrometry. Insect Biochem Mol Biol.32:331-341.
Anastopoulos, P., M. J. Thurn, and K. W. Broady.1991. Anticoagulant in the tick Ixodesholocyclus. Aust Vet J.68:366-367.
Anderson, J. F.2002. The natural history of ticks. Med Clin North Am.86:205-218.
Andrade, B. B., C. R. Teixeira, A. Barral, and M. Barral-Netto.2005. Haematophagousarthropod saliva and host defense system: a tale of tear and blood. An Acad Bras Cienc.77:665-693.
Anguita, J., N. Ramamoorthi, J. W. Hovius, S. Das, V. Thomas, R. Persinski, D. Conze, P. W.Askenase, M. Rincon, F. S. Kantor, and E. Fikrig.2002. Salp15, an Ixodes scapularissalivary protein, inhibits CD4+T cell activation. Immunity.16:849-859.
Baranton G., D. Postic, I. Saint Girons, P. Boerlin, JC. Piffaretti, M. Assous, and P. A.Grimont.1992. Delineation of Borrelia burgdorferi sensu stricto, Borrelia garinii sp.nov., and group VS461associated with lyme borreliosis. Int J Syst Bacteriol.42(3):378-383.
Bergman, D. K., M. J. Palmer, M. J. Caimano, J. D. Radolf, and S. K. Wikel.2000. Isolationand molecular cloning of a secreted immunosuppressant protein from Dermacentorandersoni salivary gland. J Parasitol.86:516-525.
Bergman, D. K., R. N. Ramachandra, and S. K. Wikel.1998. Characterization of animmunosuppressant protein from Dermacentor andersoni (Acari: Ixodidae) salivaryglands. J Med Entomol.35:505-509.
Bowman, A. S., J. R. Sauer, K. Zhu, and J. W. Dillwith.1995. Biosynthesis of salivaryprostaglandins in the lone star tick, Amblyomma americanum. Insect Biochem Mol Biol.25:735-741.
Bowman, A. S., J. W. Dillwith, and J. R. Sauer.1996. Tick salivary prostaglandins: Presence,origin and significance. Parasitol Today.12:388-396.
Breitner-Ruddock, S., R. Würzner J rg Schulze, and V. Brade.1997. Heterogeneity in thecomplement-dependent bacteriolysis within the species of Borrelia burgdorferi. MedMicrobiol Immunol.185:253-260.
Brossard, M., and S. K. Wikel.2004. Tick immunobiology. Parasitol.129Suppl: S161-176.
Burgdorfer W, A. G. Barbour, S. F. Hayes, J. L. Benach, E. Grunwaldt, and J. P. Davis.1982.Lyme disease-a tick-borne spirochetosis? Science.216(4552):1317-9.
Cavassani, K. A., J. C. Aliberti, A. R. Dias, J. S. Silva, and B. R. Ferreira.2005. Tick salivainhibits differentiation, maturation and function of murine bone-marrow-deriveddendritic cells. Immunology.114:235-245.
Champagne, D. E.2004. Antihemostatic strategies of blood-feeding arthropods. Curr DrugTargets Cardiovasc Haematol Disord.4:375-396.
Champagne, D. E.2005. Antihemostatic molecules from saliva of blood-feeding arthropods.Pathophysiol Haemost Thromb.34:221-227.
Chinery, W. A., and E. Ayitey-Smith.1977. Histamine blocking agent in the salivary glandhomogenate of the tick Rhipicephalus sanguineus sanguineus. Nature.265:366-367.
Chinzei, Y., and D. Taylor.1994. Hormonal regulation of vitellogenin biosynthesis in ticks.In: Harris KF ed. Advances in Disease Vector Research. Vol.10. Springer-Verlag, NewYork. pp.1-22.
Ciprandi, A., S. K. de Oliveira, A. Masuda, F. Horn, and C. Termignoni.2006. Boophilusmicroplus: its saliva contains microphilin, a small thrombin inhibitor. Exp Parasitol.114:40-46.
Connat, J. L., J. Ducommun, and P. A. Diehl.1983. Juvenile hormone-like substances caninduce vitellogenesis in the tick Ornithodoros moubata (Acarina: Argasidae).International Journal of Invertebrate Reproduction.6:285-294.
Daix, V., H. Schroeder, N. Praet, J. P. Georgin, I. Chiappino, L. Gillet, K. de Fays, Y.Decrem, G. Leboulle, E. Godfroid, A. Bollen, P. P. Pastoret, L. Gern, P. M. Sharp, andA. Vanderplasschen.2007. Ixodes ticks belonging to the Ixodes ricinus complex encodea family of anticomplement proteins. Insect Mol Biol.16:155-166.
Das, S., G. Banerjee, K. DePonte, N. Marcantonio, F. S. Kantor, and E. Fikrig.2001.Salp25D, an Ixodes scapularis antioxidant, is1of14immunodominant antigens inengorged tick salivary glands. J Infect Dis.184:1056-1064.
de Silva A. M., K.R. Tyson, and U. Pal.2009. Molecular characterization of the tick–Borreliainterface. Front Biosci.14:3051-3063.
Dees, W. H., D. E. Sonenshine, and E. Breidling.1984. Ecdysteroids in the American dogtick, Dermacentor variabilis (Acari: Ixodidae), during different periods of tickdevelopment. J Med Entomol.21(5):514-523.
Dennis, D. T., and J. F. Piesman.2005. Overview of tick-borne infections of humans. In Tick-Borne Diseases of Humans. J. L. Goodman, D. T. Dennis, and D. E. Sonenshine. Editors.American Society for Microbiology Press. Washingtion, D.C. pp.3-11.
Dickinson, R. G., J. E. O'Hagan, M. Schotz, K. C. Binnington, and M. P. Hegarty.1976.Prostaglandin in the saliva of the cattle tick Boophilus microplus. Aust J Exp Biol MedSci.54:475-486.
邓国藩，姜在阶.1991.中国经济昆虫志.第三十九册，蜱螨亚纲硬蜱科.北京：科学出版社.18-19.
Edwards, M. S., D. L. Kasper, H. J. Jennings, C. J. Baker, and A. Nicholson-Weller.1982.Capsular sialic acid prevents activation of the alternative complement pathway by typeIII, group B streptococci. J Immunol128:1278-1283.
Ehebauer, M. T., B. J. Mans, A. R. Gaspar, and A. W. Neitz.2002. Identification of extrinsicblood coagulation pathway inhibitors from the tick Ornithodoros savignyi (Acari:Argasidae). Exp Parasitol.101:138-148.
Fearon, D. T.1979. Regulation of the amplification C3convertase of human complement byan inhibitory protein isolated from human erythrocyte membrane. Proc Natl Acad Sci US A.76:5867-5871.
Fearon, D. T. and K. F. Austen.1975. Properdin: binding to C3b and stabilization of the C3b-dependent C3convertase. J Exp Med.142:856-863.
Ferreira, B. R. and J. S. Silva.1998. Saliva of Rhipicephalus sanguineus tick impairs T cellproliferation and IFN-gamma-induced macrophage microbicidal activity. Vet ImmunolImmunopathol.64:279-293.
Ferreira, B. R. and J. S. Silva.1999. Successive tick infestations selectively promote a T-helper2cytokine profile in mice. Immunology.96:434-439.
Ferreira, C. A., I. Da Silva Vaz, S. S. da Silva, K. L. Haag, J. G. Valenzuela, and A. Masuda.2002. Cloning and partial characterization of a Boophilus microplus (Acari: Ixodidae)calreticulin. Exp Parasitol.101:25-34.
Fine, D. P., S. R. Marney, Jr., D. G. Colley, J. S. Sergent, and R. M. Des Prez.1972. C3shuntactivation in human serum chelated with EGTA. J Immunol.109:807-809.
Forsgren, A., R. H. Mclean, A. F. Michael, and P. G. Quie.1975. Studies of the alternatepathway in chelated serum. J Lab Clin Med.85(6):904-912.
Francischetti, I. M., J. G. Valenzuela, J. F. Andersen, T. N. Mather, and J. M. Ribeiro.2002.Ixolaris, a novel recombinant tissue factor pathway inhibitor (TFPI) from the salivarygland of the tick, Ixodes scapularis: identification of factor X and factor Xa as scaffoldsfor the inhibition of factor VIIa/tissue factor complex. Blood.99:3602-3612.
Francischetti, I. M., T. N. Mather, and J. M. Ribeiro.2004. Penthalaris, a novel recombinantfive-Kunitz tissue factor pathway inhibitor (TFPI) from the salivary gland of the tickvector of Lyme disease, Ixodes scapularis. Thromb Haemost.91:886-898.
Frauenschuh, A., C. A. Power, M. Deruaz, B. R. Ferreira, J. S. Silva, M. M. Teixeira, J. M.Dias, T. Martin, T. N. Wells, and A. E. Proudfoot.2007. Molecular cloning andcharacterization of a highly selective chemokine-binding protein from the tickRhipicephalus sanguineus. J Biol Chem.282:27250-27258.
Friesen, K. J., and W. R. Kaufman.2002. Quantification of vitellogenesis and its control by20-hydroxyecdysone in the ixodid tick, Amblyomma hebraeum. J Insect Physiol.48(8):773-782.
Friesen, K. J., and W. R. Kaufman.2004. Effects of20-hydroxyecdysone and other hormoneson egg development, and identification of a vitellin-binding protein in the ovary of thetick, Amblyomma hebraeum. J Insect Physiol.50(6):519-529.
Fujita, T., T. Inoue, K. Ogawa, K. Iida, and N. Tamura.1987. The mechanism of action ofdecay-accelerating factor (DAF). DAF inhibits the assembly of C3convertases bydissociating C2a and Bb. J Exp Med.166:1221-1228.
Ganapamo, F., B. Rutti, and M. Brossard.1995. In vitro production of interleukin-4andinterferon-gamma by lymph node cells from BALB/c mice infested with nymphal Ixodesricinus ticks. Immunology.85:120-124.
Gao, J., J. Luo, R. Fan, V. Fingerle, G. Guan, Z. Liu, Y. Li, H. Zhao, M. Ma, J. Liu, A. Liu,Q. Ren, Z. Dang, C. Sugimoto, and H. Yin.2007. Cloning and characterization of acDNA clone encoding calreticulin from Haemaphysalis qinghaiensis (Acari: Ixodidae).Parasitol Res.102:737-746.
Garg, R., I. J. Juncadella, N. Ramamoorthi, Ashish, S. K. Ananthanarayanan, V. Thomas, M.Rincon, J. K. Krueger, E. Fikrig, C. M. Yengo, and J. Anguita.2006. Cutting edge: CD4is the receptor for the tick saliva immunosuppressor, Salp15. J Immunol.177:6579-6583.
Gaspar, A. R., A. M. Joubert, J. C. Crause, and A. W. Neitz.1996. Isolation andcharacterization of an anticoagulant from the salivary glands of the tick, Ornithodorossavignyi (Acari: Argasidae). Exp Appl Acarol.20:583-598.
Gillespie, R. D., M. L. Mbow, and R. G. Titus.2000. The immunomodulatory factors ofbloodfeeding arthropod saliva. Parasite Immunol.22:319-331.
Goddard, J.1993. Physician's Guide to Arthropods of Medical Importance. CRC Press, BocaRaton, FL.
Gordon, J. R. and J. R. Allen.1991. Factors V and VII anticoagulant activities in the salivaryglands of feeding Dermacentor andersoni ticks. J Parasitol.77:167-170.
Gwakisa, P., K. Yoshihara, T. Long To, H. Gotoh, F. Amano, and E. Momotani.2001.Salivary gland extract of Rhipicephalus appendiculatus ticks inhibits in vitrotranscription and secretion of cytokines and production of nitric oxide by LPS-stimulatedJA-4cells. Vet Parasitol.99:53-61.
Hajnicka, V., I. Vancova, P. Kocakova, M. Slovak, J. Gasperik, M. Slavikova, R. S. Hails, M.Labuda, and P. A. Nuttall.2005. Manipulation of host cytokine network by ticks: apotential gateway for pathogen transmission. Parasitology.130:333-342.
Hajnicka, V., P. Kocakova, M. Slavikova, M. Slovak, J. Gasperik, N. Fuchsberger, and P. A.Nuttall.2001. Anti-interleukin-8activity of tick salivary gland extracts. ParasiteImmunol.23:483-489.
Hannier, S., J. Liversidge, J. M. Sternberg, and A. S. Bowman.2004. Characterization of theB-cell inhibitory protein factor in Ixodes ricinus tick saliva: a potential role in enhancedBorrelia burgdorferi transmission. Immunology.113:401-408.
Harris, C. L., D. M. Pettigrew, S. M. Lea, and B. P. Morgan.2007. Decay-accelerating factormust bind both components of the complement alternative pathway C3convertase tomediate efficient decay. J Immunol.178:352-359.
Hiemstra, P. S., A. Gorter, M. E. Stuurman, L. A. Van Es, M. R. Daha.2005. Activation ofthe alternative pathway of complement by human serum IgA. Eur J Immunol.17(3):321-326.
Hoffmann, A., P. Walsmann, G. Riesener, M. Paintz, and F. Markwardt.1991. Isolation andcharacterization of a thrombin inhibitor from the tick Ixodes ricinus. Pharmazie.46:209-212.
Horn, F., P. C. dos Santos, and C. Termignoni.2000. Boophilus microplus anticoagulantprotein: an antithrombin inhibitor isolated from the cattle tick saliva. Arch BiochemBiophys.384:68-73.
Hourcade, D. E.2006. The role of properdin in the assembly of the alternative pathway C3convertases of complement. J Biol Chem.281:2128-32.
Hourcade, D. E., L. M. Mitchell, and M. E. Medof.1999. Decay acceleration of thecomplement alternative pathway C3convertase. Immunopharmacology.42:167-173.
Hovius, J. W., N. Ramamoorthi, C. Van't Veer, K. A. de Groot, A. M. Nijhof, F. Jongejan, A.P. van Dam, and E. Fikrig.2007. Identification of Salp15homologues in Ixodes ricinusticks. Vector Borne Zoonotic Dis.7:296-303.
Ibrahim, M. A., A. H. Ghazy, T. M. Maharem, and M. I. Khalil.2001. Factor Xa (FXa)inhibitor from the nymphs of the camel tick Hyalomma dromedarii. Comp BiochemPhysiol B Biochem Mol Biol.130:501-512.
Ibrahim, M. A., A. H. Ghazy, T. Maharem, and M. Khalil.2001. Isolation and properties oftwo forms of thrombin inhibitor from the nymphs of the camel tick Hyalommadromedarii (Acari: Ixodidae). Exp Appl Acarol.25:675-698.
Inokuma, H., D. H. Kemp, and P. Willadsen.1994. Comparison of prostaglandin E2(PGE2)in salivary gland of Boophilus microplus, Haemaphysalis longicornis and Ixodesholocyclus, and quantification of PGE2in saliva, hemolymph, ovary and gut of B.microplus. J Vet Med Sci.56:1217-1218.
Inokuma, H., T. Aita, K. Tamura, and T. Onishi.1997. Effect of infestation withRhipicephalus sanguineus on the antibody productivity in dogs. Med Vet Entomol.11:201-202.
Iwanaga, S., M. Okada, H. Isawa, A. Morita, M. Yuda, and Y. Chinzei.2003. Identificationand characterization of novel salivary thrombin inhibitors from the ixodidae tick,Haemaphysalis longicornis. Eur J Biochem.270:1926-1934.
James, A. M., X. X. Zhu, and J. H. Oliver Jr.1997. Vitellogenin and ecdysteroid titers inIxodes scapularis during vitellogenesis. J Parasitol.83(4):559-563.
Jaworski, D. C., F. A. Simmen, W. Lamoreaux, L. B. Coons, M. T. Muller, and G. RNeedham.1995. A secreted calreticulin protein in the ixodid tick (Amblyommaamericanum) saliva. J Insect Physiol.41:369-375.
Joubert, A. M., J. C. Crause, A. R. Gaspar, F. C. Clarke, A. M. Spickett, and A. W. Neitz.1995. Isolation and characterization of an anticoagulant present in the salivary glands ofthe bont-legged tick, Hyalomma truncatum. Exp Appl Acarol.19:79-92.
Juncadella, I. J., R. Garg, S. K. Ananthnarayanan, C. M. Yengo, and J. Anguita.2007. T-cellsignaling pathways inhibited by the tick saliva immunosuppressor, Salp15. FEMSImmunol Med Microbiol.49:433-438.
Kato, N., S. Iwanaga, T. Okayama, H. Isawa, M. Yuda, and Y. Chinzei.2005. Identificationand characterization of the plasma kallikrein-kinin system inhibitor, haemaphysalin,from hard tick, Haemaphysalis longicornis. Thromb Haemost.93:359-367.
Kaufman, W. R.1991. Correlation between haemolymph ecdysteroid titre, salivary glanddegeneration and ovarian development in the ixodid tick, Amblyomma hebraeum Koch.J Insect Physiol.37(2):95-99.
Kimura, Y., T. Miwa, L. Zhou, and W. C. Song.2008. Activator-specific requirement ofproperdin in the initiation and amplification of the alternative pathway complement.Blood.111:732-740.
Kirkitadze, M.D. and P. N. Barlow.2001. Structure and flexibility of the multiple domainproteins that regulate complement activation. Immunol Rev180:146-161.
Koh, C. Y., M. Kazimirova, A. Trimnell, P. Takac, M. Labuda, P. A. Nuttall, and R. M. Kini.2007. Variegin, a novel fast and tight binding thrombin inhibitor from the tropical bonttick. J Biol Chem.282:29101-29113.
Kopecky, J. and M. Kuthejlova.1998. Suppressive effect of Ixodes ricinus salivary glandextract on mechanisms of natural immunity in vitro. Parasite Immunol.20:169-174.
Kopecky, J., M. Kuthejlova, and J. Pechova.1999. Salivary gland extract from Ixodes ricinusticks inhibits production of interferon-gamma by the upregulation of interleukin-10.Parasite Immunol.21:351-356.
Kovar, L., J. Kopecky, and B. Rihova.2001. Salivary gland extract from Ixodes ricinus tickpolarizes the cytokine profile toward Th2and suppresses proliferation of T lymphocytesin human PBMC culture. J Parasitol.87:1342-1348.
Kubes, M., N. Fuchsberger, M. Labuda, E. Zuffova, and P. A. Nuttall.1994. Salivary glandextracts of partially fed Dermacentor reticulatus ticks decrease natural killer cell activityin vitro. Immunology.82:113-116.
Kubes, M., P. Kocakova, M. Slovak, M. Slavikova, N. Fuchsberger, and P. A. Nuttall.2002.Heterogeneity in the effect of different ixodid tick species on human natural killer cellactivity. Parasite Immunol.24:23-28.
Kurtenbach, K., S. De Michelis, S. Etti, S. M. Scha fer, H. S. Sewell, V. Brade, and PKraiczy.2002. Host association of Borrelia burgdorferi sensu lato—the key role of hostcomplement. Trends Microbiol.10:74–79.
Kuthejlova, M., J. Kopecky, G. Stepanova, and A. Macela.2001. Tick salivary gland extractinhibits killing of Borrelia afzelii spirochetes by mouse macrophages. Infect Immun.69:575-578.
Lawrie, C. H., R. B. Sim, and P. A. Nuttall.2005. Investigation of the mechanisms of anti-complement activity in Ixodes ricinus ticks. Mol Immunol.42:31-38.
Lawrie, C. H., S. E. Randolph, and P. A. Nuttall.1999. Ixodes ticks: serum species sensitivityof anticomplement activity. Exp Parasitol.93:207-214.
Leboulle, G., M. Crippa, Y. Decrem, N. Mejri, M. Brossard, A. Bollen, and E. Godfroid.2002. Characterization of a novel salivary immunosuppressive protein from Ixodesricinus ticks. J Biol Chem.277:10083-10089.
Limo, M. K., W. P. Voigt, A. G. Tumbo-Oeri, R. M. Njogu, and O. K. ole-MoiYoi.1991.Purification and characterization of an anticoagulant from the salivary glands of theixodid tick Rhipicephalus appendiculatus. Exp Parasitol.72:418-429.
梁茂茂.2011.蜱虫的危害及防治.吉林畜牧兽医.32(9):43-45.
李知新，刘光远，田占成，谢俊仁，王路，龚真莉，柴慧萍，孙晓林.2007.实验室条件下长角血蜱甘肃株孤雌生殖种群的生物学特性.中国兽医科学.37(4)：277-281.
Macaluso, K. R. and S. K. Wikel.2001. Dermacentor andersoni: effects of repeatedinfestations on lymphocyte proliferation, cytokine production, and adhesion-moleculeexpression by BALB/c mice. Ann Trop Med Parasitol.95:413-427.
Mans, B. J. and A. W. Neitz.2004. Adaptation of ticks to a blood-feeding environment:evolution from a functional perspective. Insect Biochem Mol Biol.34:1-17.
Mans, B. J., A. I. Louw, and A. W. Neitz.2002. Amino acid sequence and structure modelingof savignin, a thrombin inhibitor from the tick, Ornithodoros savignyi. Insect BiochemMol Biol.32:821-828.
Mans, B. J., A. R. Gaspar, A. I. Louw, and A. W. Neitz.1998. Apyrase activity and plateletaggregation inhibitors in the tick Ornithodoros savignyi (Acari: Argasidae). Exp ApplAcarol.22:353-366.
Mans, B. J., J. F. Andersen, T. G. Schwan, and J. M. Ribeiro.2008. Characterization of anti-hemostatic factors in the argasid, Argas monolakensis: Implications for the evolution ofblood-feeding in the soft tick family. Insect Biochem Mol Biol.38:22-41.
Maxwell, S. S., T. A. Stoklasek, Y. Dash, K. R. Macaluso, and S. K. Wikel.2005. Tickmodulation of the in-vitro expression of adhesion molecules by skin-derived endothelialcells. Ann Trop Med Parasitol.99:661-672.
Montgomery, R. R., D. Lusitani, A. De Boisfleury Chevance, and S. E. Malawista.2004. Ticksaliva reduces adherence and area of human neutrophils. Infect Immun.72:2989-2994.
Morgan, B. P., and C. L. Harris.1999. Complement regulatory proteins. Academic Press. SanDiego, CA.
Motoyashiki, T., A. T. Tu, D. A. Azimov, and K. Ibragim.2003. Isolation of anticoagulantfrom the venom of tick, Boophilus calcaratus, from Uzbekistan. Thromb Res.110:235-241.
Muller-Doblies, U. U. and S. K. Wikel.2005. The Human Reaction to Ticks, In Tick-BorneDiseases of Humans. J. L. Goodman, D. T. Dennis, and D. E. Sonenshine. Editors.American Society for Microbiology. Washington DC. pp.102-22.
Muller-Doblies, U. U., S. S. Maxwell, V. D. Boppana, M. A. Mihalyo, S. J. McSorley, A. T.Vella, A. J. Adler, and S. K. Wikel.2007. Feeding by the tick, Ixodes scapularis, causesCD4+T cells responding to cognate antigen to develop the capacity to express IL-4.Parasite Immunol.29:485-499.
Narasimhan, S., R. A. Koski, B. Beaulieu, J. F. Anderson, N. Ramamoorthi, F. Kantor, M.Cappello, and E. Fikrig.2002. A novel family of anticoagulants from the saliva of Ixodesscapularis. Insect Mol Biol.11:641-650.
Neeper, M. P., L. Waxman, D. E. Smith, C. A. Schulman, M. Sardana, R. W. Ellis, L. W.Schaffer, P. K. Siegl, and G. P. Vlasuk.1990. Characterization of recombinant tickanticoagulant peptide. A highly selective inhibitor of blood coagulation factor Xa. J BiolChem.265:17746-17752.
Nicholson-Weller, A., J. Burge, D. T. Fearon, P. F. Weller, and K. F. Austen.1982. Isolationof a human erythrocyte membrane glycoprotein with decay-accelerating activity for C3convertases of the complement system. J Immunol.129:184-189.
Nienaber, J., A. R. Gaspar, and A. W. Neitz.1999. Savignin, a potent thrombin inhibitorisolated from the salivary glands of the tick Ornithodoros savignyi (Acari: Argasidae).Exp Parasitol.93:82-91.
Nunn, M. A., A. Sharma, G. C. Paesen, S. Adamson, O. Lissina, A. C. Willis, and P. A.Nuttall.2005. Complement inhibitor of C5activation from the soft tick Ornithodorosmoubata. J Immunol.174:2084-2091.
Nuttall, P. A., G. C. Paesen, C. H. Lawrie, and H. Wang.2000. Vector-host interactions indisease transmission. J Mol Microbiol Biotechnol.2:381-6.
Oliveira, C. J., K. A. Cavassani, D. D. More, G. P. Garlet, J. C. Aliberti, J. S. Silva, and B. R.Ferreira.2007. Tick saliva inhibits the chemotactic function of MIP-1alpha andselectively impairs chemotaxis of immature dendritic cells by down-regulating cell-surface CCR5. Int J Parasitol.38:705–716.
Paesen, G. C., P. L. Adams, K. Harlos, P. A. Nuttall, and D. I. Stuart.1999. Tick histamine-binding proteins: isolation, cloning, and three-dimensional structure. Mol Cell.3:661-671.
Pangburn, M. K.1986. Differences between the binding sites of the complement regulatoryproteins DAF, CR1, and factor H on C3convertases. J Immunol.136(6):2216-2221.
Pangburn, M. K. and H. J. Muller-Eberhard.1986. The C3convertase of the alternativepathway of human complement. Enzymic properties of the bimolecular proteinase.Biochem J.235:723-730.
Pechova, J., J. Kopecky, and J. Salat.2004. Effect of tick salivary gland extract on thecytokine production by mouse epidermal cells. Folia Parasitol (Praha).51:367-372.
Pillemer, L., L. Blum., I. H. Lepow, O. A. Ross, E. W. Todd, and A. C. Wardlaw.1954. Theproperdin system and immunity. I. Demonstration and isolation of a new serum protein,properdin, and its role in immune phenomena. Science.120:279-285.
Ramachandra, R. N. and S. K. Wikel.1992. Modulation of host-immune responses by ticks(Acari: Ixodidae): effect of salivary gland extracts on host macrophages and lymphocytecytokine production. J Med Entomol.29:818-826.
Ramachandra, R. N. and S. K. Wikel.1995. Effects of Dermacentor andersoni (Acari:Ixodidae) salivary gland extracts on Bos indicus and B. taurus lymphocytes andmacrophages: in vitro cytokine elaboration and lymphocyte blastogenesis. J MedEntomol.32:338-345.
Ribeiro, J. M.1987. Ixodes dammini: salivary anti-complement activity. Exp Parasitol.64:347-353.
Ribeiro, J. M. and I. M. Francischetti.2003. Role of arthropod saliva in blood feeding:sialome and post-sialome perspectives. Annu Rev Entomol.48:73-88.
Ribeiro, J. M. and T. N. Mather.1998. Ixodes scapularis: salivary kininase activity is ametallo dipeptidyl carboxypeptidase. Exp Parasitol.89:213-221.
Ribeiro, J. M., F. Alarcon-Chaidez, I. M. Francischetti, B. J. Mans, T. N. Mather, J. G.Valenzuela, and S. K. Wikel.2006. An annotated catalog of salivary gland transcriptsfrom Ixodes scapularis ticks. Insect Biochem Mol Biol.36:111-129.
Ribeiro, J. M., G. T. Makoul, and D. R. Robinson.1988. Ixodes dammini: evidence forsalivary prostacyclin secretion. J Parasitol.74:1068-1069.
Ribeiro, J. M., G. T. Makoul, J. Levine, D. R. Robinson, and A. Spielman.1985.Antihemostatic, antiinflammatory, and immunosuppressive properties of the saliva of atick, Ixodes dammini. J Exp Med.161:332-344.
Ribeiro, J. M., J. J. Weis, and S. R. Telford,3rd.1990. Saliva of the tick Ixodes damminiinhibits neutrophil function. Exp Parasitol.70:382-388.
Ribeiro, J. M., P. M. Evans, J. L. MacSwain, and J. Sauer.1992. Amblyomma americanum:characterization of salivary prostaglandins E2and F2alpha by RP-HPLC/bioassay andgas chromatography-mass spectrometry. Exp Parasitol.74:112-116.
Ribeiro, J. M., T. M. Endris, and R. Endris.1991. Saliva of the soft tick, Ornithodorosmoubata, contains anti-platelet and apyrase activities. Comp Biochem Physiol A.100:109-112.
Rosell-Davis, R., and L. B. Coons.1991. Determination of vitellogenin titer in thehemolymph of Dermacentor variabilis (Acarina: Ixodidae) using an indirect enzyme-linked immunosorbent assay. J Med Entomol.28(1):41-44.
Ross, G. D., J. D. Lambris, J. A. Cain, and S. L. Newman.1982. Generation of three differentfragments of bound C3with purified factor I or serum. I. Requirements for factor H vsCR1cofactor activity. J Immunol.129:2051-2060.
Roversi, P., O. Lissina, S. Johnson, N. Ahmat, G. C. Paesen, K. Ploss, W. Boland, M. A.Nunn, and S. M. Lea.2007. The structure of OMCI, a novel lipocalin inhibitor of thecomplement system. J Mol Biol.369:784-793.
Sa-Nunes, A., A. Bafica, D. A. Lucas, T. P. Conrads, T. D. Veenstra, J. F. Andersen, T. N.Mather, J. M. Ribeiro, and I. M. Francischetti.2007. Prostaglandin E2is a majorinhibitor of dendritic cell maturation and function in Ixodes scapularis saliva. JImmunol.179:1497-1505.
Sanders, M. L., D. C. Jaworski, J. L. Sanchez, R. F. DeFraites, G. E. Glass, A. L. Scott, S.Raha, B. C. Ritchie, G. R. Needham, and B. S. Schwartz.1998. Antibody to a cDNA-derived calreticulin protein from Amblyomma americanum as a biomarker of tickexposure in humans. Am J Trop Med Hyg.59:279-285.
Schoeler, G. B. and S. K. Wikel.2001. Modulation of host immunity by haematophagousarthropods. Ann Trop Med Parasitol.95:755-771.
Schoeler, G. B., S. A. Manweiler, and S. K. Wikel.1999. Ixodes scapularis: effects ofrepeated infestations with pathogen-free nymphs on macrophage and T lymphocytecytokine responses of BALB/c and C3H/HeN mice. Exp Parasitol.92:239-248.
Schoeler, G. B., S. A. Manweiler, and S. K. Wikel.2000. Cytokine responses of C3H/HeNmice infested with Ixodes scapularis or Ixodes pacificus nymphs. Parasite Immunol.22:31-40.
Schuijt, T. J., J. Coumou, S. Narasimhan, J. Dai, K. DePonte, D. Wouters, M. Brouwer, A.Oei, J. J.T.H. Roelofs, A. P. van Dam, T. van der Poll, C. van't Veer, J. W. Hovius, andE. Fikrig.2011. A Tick mannose-binding lectin inhibitor interferes with the vertebratecomplement cascade to enhance transmission of the Lyme disease agent. Cell HostMicrobe.10:136-146.
Schwaeble, W., H. P. Huemer, J. M st, M. P. Dierich, M. Str bel, C. Claus, K. B. Reid, andH. W. Ziegler-Heitbrock.1994. Expression of properdin in human monocytes. Eur JBiochem.219:759-764.
Schwaeble, W., W. Schwaeble, W. G. Dippold, M. K. Sch fer, H. Pohla, D. Jonas, Luttig B,Weihe E, H. P. Huemer, M. P. Dierich, and K. B. Reid.1993. Properdin, a positiveregulator of complement activation, is expressed in human T cell lines and peripheralblood T cells. J Immunol.151:2521-2528.
Seixas, A., K. J. Friesen, and W. R. Kaufman.2008. Effect of20-hydroxyecdysone andhaemolymph on oogenesis in the ixodid tick Amblyomma hebraeum. J Insect Physiol.54:1175-1183.
Seya, T. and J. P. Atkinson.1989. Functional properties of membrane cofactor protein ofcomplement. Biochem J.264:581-588.
Seya, T., J. R. Turner, and J. P. Atkinson.1986. Purification and characterization of amembrane protein (gp45-70) that is a cofactor for cleavage of C3b and C4b. J Exp Med.163:837-855.
Soares, C. A., C. M. Lima, M. C. Dolan, J. Piesman, C. B. Beard, and N. S. Zeidner.2005.Capillary feeding of specific dsRNA induces silencing of the isac gene in nymphalIxodes scapularis ticks. Insect Mol Biol.14:443-452.
Sonenshine, D. E.2005. The Biology of Tick Vectors of Human Disease, In Tick-BorneDiseases of Humans. J. L. Goodman, D. T. Dennis, and D. E. Sonenshine. Editors.American Society for Microbiology Press. Washington, DC. pp.12-35.
Sonenshine, D. E.,1991. Biology of Ticks. Oxford University Press. New York, NY.
Spitzer, D., L. M. Mitchell, J. P. Atkinson, and D. E. Hourcade.2007. Properdin can initiatecomplement activation by binding specific target surfaces and providing a platform forde novo convertase assembly. J Immunol.179:2600-2608.
Stover, C. M., J. C. Luckett, B. Echtenacher, A. Dupont, S. E. Figgitt, J. Brown, D. N.M nnel, and W. J. Schwaeble.2008. Properdin plays a protective role in polymicrobialseptic peritonitis. J Immunol.180:3313-3318.
Tanaka, A. S., R. Andreotti, A. Gomes, R. J. Torquato, M. U. Sampaio, and C. A. Sampaio.1999. A double headed serine proteinase inhibitor—human plasma kallikrein andelastase inhibitor—from Boophilus microplus larvae. Immunopharmacology.45:171-177.
Taylor D., A. Moribayashi, N. Agui, T. Shono, and Y. Chinzei.1997. Hormonal regulation ofvitellogenesis in the soft tick, Ornithodoros moubata. S. Kawashima and S. Kikuyama.Editors. Advances in Comparative Endocrinology. Monduzzi Editore. Bologna. Italy. pp.213-220.
Thompson D. M., S. M. S. Khalil, L. A. Jeffers, U. Ananthapadmanaban, D. E. Sonenshine,R. D. Mitchell, C. J. Osgood, C. S. Apperson, R. M. Roe.2005. In vivo role of20-hydroxyecdysone in the regulation of the vitellogenin mRNA and egg development inthe American dog tick, Dermacentor variabilis. J Insect Physiol.51(10):1105-1116.
Titus, R. G., J. V. Bishop, and J. S. Mejia.2006. The immunomodulatory factors of arthropodsaliva and the potential for these factors to serve as vaccine targets to prevent pathogentransmission. Parasite Immunol.28:131-141.
Tsuji, N., T. Kamio, T. Isobe, and K. Fujisaki.2001. Molecular characterization of aperoxiredoxin from the hard tick Haemaphysalis longicornis. Insect Mol Biol.10:121-129.
Tyson, K. R., C. Elkins, and A. M. de Silva.2008. A novel mechanism of complementinhibition unmasked by a tick salivary protein that binds to properdin. J Immunol.180:3964-3968.
Tyson, K., C. Elkins, H. Patterson, E. Fikrig and A. de Silva.2007. Biochemical andfunctional characterization of Salp20, an Ixodes scapularis complement pathway. InsectMol Biol.16(4):469-479.
Urioste, S., L. R. Hall, S. R. Telford,3rd, and R. G. Titus.1994. Saliva of the Lyme diseasevector, Ixodes dammini, blocks cell activation by a nonprostaglandin E2-dependentmechanism. J Exp Med.180:1077-1085.
Valenzuela, J. G.2004. Exploring tick saliva: from biochemistry to 'sialomes' and functionalgenomics. Parasitology.129Suppl: S83-94.
Valenzuela, J. G., I. M. Francischetti, V. M. Pham, M. K. Garfield, T. N. Mather, and J. M.Ribeiro.2002. Exploring the sialome of the tick Ixodes scapularis. J Exp Biol.205:2843-2864.
Valenzuela, J. G., R. Charlab, T. N. Mather, and J. M. Ribeiro.2000. Purification, cloning,and expression of a novel salivary anticomplement protein from the tick, Ixodesscapularis. J Biol Chem.275:18717-18723.
van Dam, A.P., A. Oei, R. Jaspars, C. Fijen, B. Wilske, L. Spanjaard, and J. Dankert.1997.Complement-mediated serum sensitivity among spiro-chetes that cause Lyme disease.Infect Immun.65:1228-1236.
van de Locht, A., M. T. Stubbs, W. Bode, T. Friedrich, C. Bollschweiler, W. Hoffken, and R.Huber.1996. The ornithodorin-thrombin crystal structure, a key to the TAP enigma?Embo J.15:6011-6017.
Vancova, I., M. Slovak, V. Hajnicka, M. Labuda, L. Simo, K. Peterkova, R. S. Hails, and P.A. Nuttall.2007. Differential anti-chemokine activity of Amblyomma variegatum adultticks during blood-feeding. Parasite Immunol.29:169-177.
Wang, H. and P. A. Nuttall.1994. Excretion of host immunoglobulin in tick saliva anddetection of IgG-binding proteins in tick haemolymph and salivary glands. Parasitology.109(4):525-530.
Wang, H. and P. A. Nuttall.1995. Immunoglobulin G binding proteins in male Rhipicephalusappendiculatus ticks. Parasite Immunol.17:517-524.
Wang, H., and P. A. Nuttall.1995. Immunoglobulin-G binding proteins in the ixodid ticks,Rhipicephalus appendiculatus, Amblyomma variegatum and Ixodes hexagonus.Parasitology.111(2):161-165.
Waxman, L., D. E. Smith, K. E. Arcuri, and G. P. Vlasuk.1990. Tick anticoagulant peptide(TAP) is a novel inhibitor of blood coagulation factor Xa. Science.248:593-596.
Weiler, J. M., M. R. Daha, K. F. Austen, and D. T. Fearon.1976. Control of the amplificationconvertase of complement by the plasma protein beta1H. Proc Natl Acad Sci U S A.73:3268-3272.
Whaley, K. and S. Ruddy.1976. Modulation of the alternative complement pathways by beta1H globulin. J Exp Med.144(5):1147-1163.
Wikel, S. K.1985. Effects of tick infestation on the plaque-forming cell response to a thymicdependent antigen. Ann Trop Med Parasitol.79:195-198.
Wikel, S. K.1996. Host immunity to ticks. Annu Rev Entomol.41:1-22.
Wikel, S. K.1999. Tick modulation of host immunity: an important factor in pathogentransmission. Int J Parasitol.29:851-9.
Xu, G., Q. Q. Fang, J. E. Keirans, and L. A. Durden.2004. Cloning and sequencing ofputative calreticulin complementary DNAs from four hard tick species. J Parasitol.90:73-78.
Yu, D., J. Liang, H. Yu, H. Wu, C. Xu, J. Liu, and R. Lai.2006. A tick B-cell inhibitoryprotein from salivary glands of the hard tick, Hyalomma asiaticum asiaticum. BiochemBiophys Res Commun.343:585-590.
Ze Chen, Xiaojun Yang, Fengju Bu, Xiaohong Yang, and Jingze Liu.2012. Morphological,biological and molecular characteristics of bisexual and parthenogenetic Haemaphysalislongicornis. Vet Parasitol.189(2012):344-352.
Zhu, K., A. S. Bowman, D. L. Brigham, R. C. Essenberg, J. W. Dillwith, and J. R. Sauer.1997. Isolation and characterization of americanin, a specific inhibitor of thrombin, fromthe salivary glands of the lone star tick Amblyomma americanum. Exp Parasitol.87:30-38.
Zhu, K., J. R. Sauer, A. S. Bowman, and J. W. Dillwith.1997. Identification andcharacterization of anticoagulant activities in the saliva of the lone star tick, Amblyommaamericanum. J Parasitol.83:38-43.
Zipfel, P. F., T. S. Jokiranta, J. Hellwage, V. Koistinen, and S. Meri.1999. The factor Hprotein family. Immunopharmacology.42:53-60.
周金林，周勇志，龚海燕，陈灵芝，曹杰.2004.我国长角血蜱孤雌生殖种群的发现和生物学特性的研究.中国媒介生物学及控制杂志.15(003)：173-174.