硬骨鱼类补体关键因子C1q及免疫球蛋白分子克隆、进化和功能的初步研究
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摘要
本论文对斑马鱼中补体经典途径中关键基因C1q以及免疫球蛋白基因进行了鉴定、功能以及进化的研究,共分为两个部分内容。第一部分应用生物信息学方法,利用基因组和EST数据库,在斑马鱼(Danio rerio)中成功预测并克隆了补体经典途径的关键基因C1q的C1qA、C1qB、C1qC三个亚基编码基因,并结合哺乳动物、软骨鱼以及七鳃鳗(Lamprey)发现中报道的C1q基因,对它们进行了基因结构与分子进化等分析。同时,在硬骨鱼中对整个C1q家族成员进行了进化分析,提出了C1q家族和EMU家族存在进化关系。另外,利用原核表达系统表达了斑马鱼C1qA、C1qB和C1qC头部结构域蛋白,研究了它们在补体经典途径中的作用。研究显示,斑马鱼C1qA、C1qB和C1qC并能和体外聚合的斑马鱼IgM重链恒定区结合,但是不能结合体外聚合的IgZ重链恒定区。在以鲫鱼血清为材料进行的补体经典途径研究表明,鱼类中存在补体经典途径,并且C1qA、C1qB和C1qC分子均参与经典途径。此外,鱼类C1qA、C1qB和C1qC还能与人热聚的IgM和IgG结合,鱼类C1qA、C1qB和C1qC的头部结构域能竞争性抑制兔C1q介导的经典途径引起的溶血反应。
第二部分克隆了多个斑马鱼免疫球蛋白基因,包括已知的IgM,IgZ基因和另外两个新的免疫球蛋白基因,其中之一与斑马鱼IgZ有一定相似性,称为IgZ-2基因,另一个为由IgM的膜型外显子直接与CH1末端连接的分子,对它们进行了生物信息学分析,在mRNA水平检测了IgZ-2在斑马鱼各个器官以及受精卵各个发育的表达情况,结果表明,IgZ-2主要表达于头肾、肠和皮肤,在受精卵发育的14天开始表达。
C1q分子是补体分子经典途径的起始分子,补体经典途径起始于C1q的两个或多个球形头部和免疫复合物中的IgM或IgG分子结合。本文首次克隆了斑马鱼C1q的三个分子C1qA、C1qB和C1qC以及斑马鱼的免疫球蛋白分子,对它们进行了生物信息学分析,并用Elisa分析了C1q和免疫球蛋白之间的关系。通过对硬骨鱼补体经典途径的研究显示,硬骨鱼中存在和哺乳动物类似的补体经典途径,硬骨鱼的C1q在补体经典途径中发挥与人C1q相似的功能。
This article focused on the molecular identification,functional characterization, and evolution analysis of complement component C1q genes and immunoglobulin genes in teleost fish.
In part one,based on the bioinformatics method such as synteny comparative analysis approach,we successfully identified and cloned the C1qA,B,C chains in Zebrafish(Danio rerio).The gene expression profiling in different tissues were detected.It was found that these genes are globally expressed and the mRNA expressions of Zebrafish C1qA could be detected at all stages during the development. Furthermore,the evolution analysis was performed the elucidate the evolution relationships of C1q family members in teleost fish such as Zebrafish(Danio rerio), Fugu(Fugu rubripe) and Tetraodon(Tetraodon nigroviridis),as well as in other vertebrate species.By phylogenetic analysis,we revealed an evolutionary relationship between C1q and EMu superfamily.Finally,utilizing the soluble recombinant protein which expressed in E.coli,we analyzed the functional characterization of the globular head regions of C1qA(ghA),B(ghB),and C(ghC) chains.The results showed that the ghA,ghB and ghC could bind to heat-aggregated human IgM and IgG and inhibit C1q mediated complement classical pathway.Moreover,it could bind to heat-aggregated and cross linked zebrafish IgM,but it could not bind to cross linked zebrafish IgZ.
In part two,we cloned multiple immunoglobulin genes in zebrafish.Two genes, named IgM and IgZ,have been reported previously.And the other two novel immunoglobulin genes,including IgZ-2 and IgMm2,were identified for the first time. According to the structure characterizations,the IgMm2 gene was supposed to be formed by the directly splicing of the transmemebrane region to CH1 of IgM.The IgZ-2 showed high homologies to the newly identified IgZ.It was expressed in the kidney,skin,and intestine and we hypothesis that it may related to mucosal immunity. It was firstly appeared 14 days after fertilization.
C1q is the first subcomponent of the classical pathway of complement activation and a major connecting link between classical pathway-driven innate immunity and IgG- or IgM- mediated acquired immunity.It could activate the classical complement pathway via binding of its globular heads to the Fc regions of aggregated IgG or IgM. In the present study,we cloned the C1qA,C1qB,and C1qC chain in zebrafish fish for the first time.Also,we identified several immunoglobulin genes in zebrafish.Thus, we performed an ELISA analysis to find a relationship between C1q and immunoglobulins and studied the classical pathway in teleost fish.In teleost fish,the classical pathway was identified,which showed similar properties as it in the mammals.And the C1q in teleost fish also has the similar functional characterizations as its mammalian counterpart.
第二部分克隆了多个斑马鱼免疫球蛋白基因,包括已知的IgM,IgZ基因和另外两个新的免疫球蛋白基因,其中之一与斑马鱼IgZ有一定相似性,称为IgZ-2基因,另一个为由IgM的膜型外显子直接与CH1末端连接的分子,对它们进行了生物信息学分析,在mRNA水平检测了IgZ-2在斑马鱼各个器官以及受精卵各个发育的表达情况,结果表明,IgZ-2主要表达于头肾、肠和皮肤,在受精卵发育的14天开始表达。
C1q分子是补体分子经典途径的起始分子,补体经典途径起始于C1q的两个或多个球形头部和免疫复合物中的IgM或IgG分子结合。本文首次克隆了斑马鱼C1q的三个分子C1qA、C1qB和C1qC以及斑马鱼的免疫球蛋白分子,对它们进行了生物信息学分析,并用Elisa分析了C1q和免疫球蛋白之间的关系。通过对硬骨鱼补体经典途径的研究显示,硬骨鱼中存在和哺乳动物类似的补体经典途径,硬骨鱼的C1q在补体经典途径中发挥与人C1q相似的功能。
This article focused on the molecular identification,functional characterization, and evolution analysis of complement component C1q genes and immunoglobulin genes in teleost fish.
In part one,based on the bioinformatics method such as synteny comparative analysis approach,we successfully identified and cloned the C1qA,B,C chains in Zebrafish(Danio rerio).The gene expression profiling in different tissues were detected.It was found that these genes are globally expressed and the mRNA expressions of Zebrafish C1qA could be detected at all stages during the development. Furthermore,the evolution analysis was performed the elucidate the evolution relationships of C1q family members in teleost fish such as Zebrafish(Danio rerio), Fugu(Fugu rubripe) and Tetraodon(Tetraodon nigroviridis),as well as in other vertebrate species.By phylogenetic analysis,we revealed an evolutionary relationship between C1q and EMu superfamily.Finally,utilizing the soluble recombinant protein which expressed in E.coli,we analyzed the functional characterization of the globular head regions of C1qA(ghA),B(ghB),and C(ghC) chains.The results showed that the ghA,ghB and ghC could bind to heat-aggregated human IgM and IgG and inhibit C1q mediated complement classical pathway.Moreover,it could bind to heat-aggregated and cross linked zebrafish IgM,but it could not bind to cross linked zebrafish IgZ.
In part two,we cloned multiple immunoglobulin genes in zebrafish.Two genes, named IgM and IgZ,have been reported previously.And the other two novel immunoglobulin genes,including IgZ-2 and IgMm2,were identified for the first time. According to the structure characterizations,the IgMm2 gene was supposed to be formed by the directly splicing of the transmemebrane region to CH1 of IgM.The IgZ-2 showed high homologies to the newly identified IgZ.It was expressed in the kidney,skin,and intestine and we hypothesis that it may related to mucosal immunity. It was firstly appeared 14 days after fertilization.
C1q is the first subcomponent of the classical pathway of complement activation and a major connecting link between classical pathway-driven innate immunity and IgG- or IgM- mediated acquired immunity.It could activate the classical complement pathway via binding of its globular heads to the Fc regions of aggregated IgG or IgM. In the present study,we cloned the C1qA,C1qB,and C1qC chain in zebrafish fish for the first time.Also,we identified several immunoglobulin genes in zebrafish.Thus, we performed an ELISA analysis to find a relationship between C1q and immunoglobulins and studied the classical pathway in teleost fish.In teleost fish,the classical pathway was identified,which showed similar properties as it in the mammals.And the C1q in teleost fish also has the similar functional characterizations as its mammalian counterpart.
引文
Al-Sharif, W. Z., Sunyer, J. O., Lambris, J. D., and Smith, L. C. (1998). Sea urchin coelomocytes specifically express a homologue of the complement component C3. J Immunol 160,2983-97.
Arlaud, G. J., Colomb, M. G., and Gagnon, J. (1987a). A functional model of the human C1 complex. Immunol. Today 8,106-111.
Arlaud, G. J., Gaboriaud, C., Thielens, N. M., Budayova-Spano, M., Rossi, V., and Fontecilla-Camps, J. C. (2002). Structural biology of the Cl complex of complement unveils the mechanisms of its activation and proteolytic activity. Mol Immunol 39, 383-94.
Bang, J. D., Kim, J. W., Lee, S. D., Park, S. I., Chun, S. G., S., J. C., and W., P. J. (1996a). Humoral immune response of flounder to Edwardsiella tarda: the presence of various sizes of immunoglobulins in flounder. Dis. quat. Organ. 26,197-203.
Bang, J. D., W., K. J., D., L. S., I., P. S., G., C. S., S., J. C., and W., P. J. (1996b). Humoral immune response of flounder to Edwardsiella tarda : the presence of various sizes of immunoglobulins in flounder. Dis. Aquat. Org. 26,197-203.
Bohlson, S. S., Fraser, D. A., and Tenner, A. J. (2007). Complement proteins C1q and MBL are pattern recognition molecules that signal immediate and long-term protective immune functions. Mol Immunol 44, 33-43.
Bork, P., and Bairoch, A. (1995). Extracellular modules. Trends Biochem. Sci. 20 (Suppl.), C03.
Boshra, H., Gelman, A. E., and Sunyer, J. O. (2004). Structural and functional characterization of complement C4 and C1s-like molecules in teleost fish: insights into the evolution of classical and alternative pathways. J Immunol 173,349-59.
Danilova, N., Bussmann, J., Jekosch, K., and Steiner, L. A. (2005). The immunoglobulin heavy-chain locus in zebrafish: identification and expression of a previously unknown isotype, immunoglobulin Z. Nat Immunol 6,295-302.
Dodds, A. W., and Matsushita, M. (2007). The phylogeny of the complement system and the origins of the classical pathway. Immunobiology 212,233-43.
Duncan, A. R., and Winter, G. (1988). The binding site for C1q on IgG. Nature 332, 738-740. Elcombe, B. M., Chang, R. J., Taves, C. J., and Winkelhake, J. L. (1985). Evolution of antibody structure and effector functions: comparative hemolytic activities of monomeric and tetrameric IgM from rainbow trout, Salmo gairdnerii. Comp Biochem Physiol B 80, 697-706.
Endo, Y., Nonaka, ML, Saiga, H., Kakinuma, Y., Matsushita, A., Takahashi, M., Matsushita, M., and Fujita, T. (2003). Origin of mannose-binding lectin-associated serine protease (MASP)-1 and MASP-3 involved in the lectin complement pathway traced back to the invertebrate, amphioxus. J Immunol 170,4701-7.
Endo, Y, Takahashi, M., and Fujita, T. (2006). Lectin complement system and pattern recognition. Immunobiology 211, 283-93.
Endo, Y., Takahashi, M., Nakao, M., Saiga, H., Sekine, H., Matsushita, M., Nonaka, M., and Fujita, T. (1998). Two lineages of mannose-binding lectin-associated serine protease (MASP) in vertebrates. J Immunol 161,4924-30.
Fairies, T. C., and Atkinson, J. P. (1991). Evolution of the complement system. Immunol Today 12, 295-300.
Flexner, S., and Noguchi, H. (1903). Snake venom in relation to haemolysis, bacteriolysis and toxicity. J.Exp.Med. 6,277-301.
Franchini, S., Zarkadis, I. K., Sfyroera, G., Sahu, A., Moore, W. T., Mastellos, D., LaPatra, S. E., and Lambris, J. D. (2001). Cloning and purification of the rainbow trout fifth component of complement (C5). Dev Comp Immunol 25,419-30.
Fujii, T., and Murakawa, S. (1981). Immunity in lamprey. III. Occurrence of the complement-like activity. Dev Comp Immunol 5,251-9.
Fujii, T., Nakamura, T., Sekizawa, A., and Tomonaga, S. (1992). Isolation and characterization of a protein from hagfish serum that is homologous to the third component of the mammalian complement system. J Immunol 148,117-23.
Fujita, T. (2002). Evolution of the lectin-complement pathway and its role in innate immunity. Nat Rev Immunol 2, 346-53.
Gasque, P. (2004). Complement: a unique innate immune sensor for danger signals. Mol Immunol 41, 1089-98.
Goh, C. S., Bogan, A. A., Joachimiak, M., Walther, D., and Cohen, F. E. (2000). Co-evolution of proteins with their interaction partners. J Mol Biol 299, 283-93.
Goh, C. S., and Cohen, F. E. (2002). Co-evolutionary analysis reveals insights into protein-protein interactions. J Mol Biol 324,177-92.
Hanley, P. J., Hook, J. W., Raftos, D. A., Gooley, A. A., Trent, R., and Raison, R. L. (1992). Hagfish humoral defense protein exhibits structural and functional homology with mammalian complement components. Proc Natl Acad Sci U S A 89, 7910-4.
Hansen, J. D., Landis, E. D., and Phillips, R. B. (2005). Discovery of a unique Ig heavy-chain isotype (IgT) in rainbow trout: Implications for a distinctive B cell developmental pathway in teleost fish. Proc Natl Acad Sci U S A 102,6919-24.
Holland, M. C., and Lambris, J. D. (2002). The complement system in teleosts. Fish Shellfish Immunol 12, 399-420.
Ishiguro, H., Kobayashi, K., Suzuki, M., Titani, K., Tomonaga, S., and Kurosawa, Y. (1992). Isolation of a hagfish gene that encodes a complement component. Embo J 11, 829-37.
Ji, X., Azumi, K., Sasaki, M., and Nonaka, M. (1997). Ancient origin of the complement lectin pathway revealed by molecular cloning of mannan binding protein-associated serine protease from a urochordate, the Japanese ascidian, Halocynthia roretzi. Proc Natl Acad Sci U S A 94, 6340-5.
Ji, X., Namikawa-Yamada, C., Nakanishi, M., Sasaki, M., and Nonaka, M. (2000). Molecular cloning of complement factor B from a solitary ascidian: unique combination of domains implicating ancient exon shufflings. Immunopharmacology 49,43.
Kaul, M., and Loos, M. (1993). The Fc-recognizing, collagen-like C1q molecule is a putative type II membrane protein of macrophages. Behring Inst Mitt, 171-9.
Kenjo, A., Takahashi, M., Matsushita, M., Endo, Y., Nakata, M., Mizuochi, T., and Fujita, T. (2001). Cloning and characterization of novel ficolins from the solitary ascidian, Halocynthia roretzi. J Biol Chem 276,19959-65.
Kishore, U., Gaboriaud, C., Waters, P., Shrive, A. K., Greenhough, T. J., Reid, K. B., Sim, R. B., and Arlaud, G. J. (2004). C1q and tumor necrosis factor superfamily: modularity and versatility. Trends Immunol 25, 551-61.
Kishore, U., Gupta, S. K., Perdikoulis, M. V., Kojouharova, M. S., Urban, B. C., and Reid, K. B. M. (2003). Modular organization of the carboxy-terminal, globular head region of human C1q A, B and C chains. J. Immunol 171, 812-820.
Kishore, U., Kojouharova, M. S., and Reid, K. B. (2002). Recent progress in the understanding of the structure-function relationships of the globular head regions of C1q. Immunobiology 205, 355-64.
Kishore, U., and Reid, K. B. (2000). C1q: structure, function, and receptors. Immunopharmacology 49, 159-70.
Kishore, U., and Reid, K. B. M. (1999). Modular organization of proteins containing C1q-like globular domains.. Immunopharmacol. 41,15-21.
Kocabas, A. M., Li, P., Cao, D., Karsi, A., He, C., Patterson, A., Ju, Z., Dunham, R. A., and Liu, Z. (2002). Expression profile of the channel catfish spleen: analysis of genes involved in immune functions. Mar Biotechnol (NY) 4, 526-36.
Koppenheffer, T. L., Spong, K. D., and Falvo, H. M. (1998). The complement system of the marsupial Monodelphis domestica. Dev Comp Immunol 22,231-7.
Leimeister, C., Steidl, C., Schumacher, N., Erhard, S., and Gessler, M. (2002). Developmental expression and biochemical characterization of Emu family members. Dev Biol 249, 204-18.
Lobb, C. J., and Olson, M. O. (1988). Immunoglobulin heavy H chain isotypes in a teleost fish. J Immunol 141,1236-45.
Maeurer, M. J., Trinder, P. K., Storkel, S., and Loos, M. (1993). C1q in autoimmune diseases: rheumatoid arthritis. Behring Inst Mitt, 262-78.
Magnadottir, B. (2000). The spontaneous haemolytic activity of cod serum: heat insensitivity and other characteristics. Fish Shellfish Immunol 10,731-5.
Magnadottir, B., Jonsdottir, H., Helgason, S., Bjornsson, B., Jorgensen, T. O., and Pilstrom, L. (1999a). Humoral immune parameters in Atlantic cod (Gadus morhua L.) I. The effects of environmental temperature. Comp Biochem Physiol B Biochem Mol Biol 122,173-80.
Magnadottir, B., Jonsdottir, H., Helgason, S., Bjornsson, B., Jorgensen, T. O., and Pilstrom, L. (1999b). Humoral immune parameters in Atlantic cod (Gadus morhua L.) II. The effects of size and gender under different environmental conditions. Comp Biochem Physiol B Biochem Mol Biol 122,181-8.
Magnadottir, B., Jonsdottir, H., Helgason, S., Bjornsson, B., Solem, S. T., and Pilstrom, L. (2001). Immune parameters of immunised cod (Gadus morhua L.). Fish Shellfish Immunol 11,75-89.
Marshall, H. T. (1904). Studies in haemolysis with special reference to the properties of blood and body fluids of Human beings. J. Exp. Med. 6, 309-332.
Matsushita, M., Matsushita, A., Endo, Y., Nakata, M., Kojima, N., Mizuochi, T., and Fujita, T. (2004). Origin of the classical complement pathway: Lamprey orthologue of mammalian C1q acts as a lectin. Proc Natl Acad Sci U S A 101,10127-31.
McNabb, T., Koh, T. Y., Dorrington, K. J., and Painter, R. H. (1976). Structure and function of immunoglobulin domains. V. Binding, University of immunoglobulin G and fragments to placental membrane preparations. J Immunol 117,882-8.
Mei, J., and Gui, J. (2008). Bioinformatic identification of genes encoding C1q-domain-containing proteins in zebrafish. J Genet Genomics 35, 17-24.
Nakao, M., Fushitani, Y., Fujiki, K., Nonaka, M., and Yano, T. (1998). Two diverged complement factor B/C2-like cDNA sequences from a teleost, the common carp (Cyprinus carpio). J Immunol 161,4811-8.
Nakao, M., Mutsuro, J., Obo, R., Fujiki, K., Nonaka, M., and Yano, T. (2000). Molecular cloning and protein analysis of divergent forms of the complement component C3 from a bony fish, the common carp (Cyprinus carpio): presence of variants lacking the catalytic histidine. Eur J Immunol 30, 858-66.
Nakao, M., and Yano, T. (1998). Structural and functional identification of complement components of the bony fish, carp (Cyprinus carpio). Immunol Rev 166,27-38.
Nonaka, M. (2001). Evolution of the complement system. Curr Opin Immunol 13, 69-73.
Nonaka, M., Azumi, K., Ji, X., Namikawa-Yamada, C., Sasaki, M., Saiga, H., Dodds, A. W., Sekine, H., Homma, M. K., Matsushita, M., Endo, Y., and Fujita, T. (1999). Opsonic complement component C3 in the solitary ascidian, Halocynthia roretzi. J Immunol 162,387-91.
Nonaka, M., Fujii, T., Kaidoh, T., Natsuume-Sakai, S., Nonaka, M., Yamaguchi, N., and Takahashi, M. (1984). Purification of a lamprey complement protein homologous to the third component of the mammalian complement system. J Immunol 133,3242-9.
Nonaka, M., Kuroda, N., Naruse, K., and Shima, A. (1998). Molecular genetics of the complement C3 convertases in lower vertebrates. Immunol Rev 166, 59-65.
Nonaka, M., Natsuume-Sakai, S., and Takahashi, M. (1981a). The complement system in rainbow trout (Salmo gairdneri). II. Purification and characterization of the fifth component (C5). J Immunol 126,1495-8.
Nonaka, M., Nonaka, M., Irie, M., Tanabe, K., Kaidoh, T., Natsuume-Sakai, S., and Takahashi, M. (1985). Identification and characterization of a variant of the third component of complement (C3) in rainbow trout (Salmo gairdneri) serum. J Biol Chem 260, 809-15.
Nonaka, M., and Smith, S. L. (2000). Complement system of bony and cartilaginous fish. Fish Shellfish Immunol 10, 215-28.
Nonaka, M., and Takahashi, M. (1992). Complete complementary DNA sequence of the third component of complement of lamprey. Implication for the evolution of thioester containing proteins. J Immunol 148, 3290-5.
Nonaka, M., Takahashi, M., and Sasaki, M. (1994). Molecular cloning of a lamprey homologue of the mammalian MHC class III gene, complement factor B. J Immunol 152,2263-9.
Nonaka, M., Yamaguchi, N., Natsuume-Sakai, S., and Takahashi, M. (1981b). The complement system of rainbow trout (Salmo gairdneri). I. Identification of the serum lytic system homologous to mammalian complement. J Immunol 126,1489-94.
Nonaka, M., and Yoshizaki, F. (2004). Evolution of the complement system. Mol Immunol 40, 897-902.
Reid, K. B. M., and Porter, R. R. (1976). Subunit composition and structure of subcomponent C1q of the first component of human complement. Biochem. J. 155,19-23.
Rombout, J. H., Taverne, N., van de Kamp, M., and Taverne-Thiele, A. J. (1993). Differences in mucus and serum immunoglobulin of carp (Cyprinus carpio L.). Dev Comp Immunol 17, 309-17.
Savan, R., Aman, A., Nakao, M., Watanuki, H., and Sakai, M. (2005a). Discovery of a novel immunoglobulin heavy chain gene chimera from common carp (Cyprinus carpio L.). Immunogenetics 57, 458-63.
Savan, R., Aman, A., Sato, K., Yamaguchi, R., and Sakai, M. (2005b). Discovery of a new class of immunoglobulin heavy chain from fugu. Eur J Immunol 35,3320-31.
Sekine, H., Kenjo, A., Azumi, K., Ohi, G., Takahashi, M., Kasukawa, R., Ichikawa, N., Nakata, M., Mizuochi, T., Matsushita, M., Endo, Y., and Fujita, T. (2001). An ancient lectin-dependent complement system in an ascidian: novel lectin isolated from the plasma of the solitary ascidian, Halocynthia roretzi. J Immunol 167,4504-10.
Shulman, M. J., Collins, C., Pennell, N., and Hozumi, N. (1987). Complement activation by IgM: evidence for the importance of the third constant domain of the mu heavy chain. Eur J Immunol 17, 549-54.
Smith, L. C., Azumi, K., and Nonaka, M. (1999). Complement systems in invertebrates. The ancient alternative and lectin pathways. Immunopharmacology 42,107-20.
Smith, L. C., Chang, L., Britten, R. J., and Davidson, E. H. (1996). Sea urchin genes expressed in activated coelomocytes are identified by expressed sequence tags. Complement homologues and other putative immune response genes suggest immune system homology within the deuterostomes. J Immunol 156, 593-602.
Smith, L. C., Shih, C. S., and Dachenhausen, S. G. (1998). Coelomocytes express SpBf, a homologue of factor B, the second component in the sea urchin complement system. J Immunol 161, 6784-93.
Smith, S. L. (1998). Shark complement: an assessment. Immunol Rev 166, 67-78.
Sunyer JO, and JD, L. (1999). "Encyclopedia of life sciences." Macmillan References Limited,
Sunyer, J. O., and Lambris, J. D. (1998). Evolution and diversity of the complement system of poikilothermic vertebrates. Immunol Rev 166,39-57.
Sunyer, J. O., Tort, L., and Lambris, J. D. (1997). Diversity of the third form of complement, C3, in fish: functional characterization of five forms of C3 in the diploid fish Sparus aurata. Biochem J 326(Pt 3), 877-81.
Sunyer, J. O., Zarkadis, I., Sarrias, M. R., Hansen, J. D., and Lambris, J. D. (1998). Cloning, structure, and function of two rainbow trout Bf molecules. J Immunol 161,4106-14.
Sunyer, J. O., Zarkadis, I. K., Sahu, A., and Lambris, J. D. (1996). Multiple forms of complement C3 in trout that differ in binding to complement activators. Proc Natl Acad Sci U S A 93, 8546-51.
Suzuki, M. M., Satoh, N., and Nonaka, M. (2002). C6-like and C3-like molecules from the cephalochordate, amphioxus, suggest a cytolytic complement system in invertebrates. J Mol Evol 54,671-9.
Terado, T., Nonaka, M. I., Nonaka, M., and Kimura, H. (2002). Conservation of the modular structure of complement factor I through vertebrate evolution. Dev Comp Immunol 26,403-13.
Terado, T., Okamura, K., Ohta, Y., Shin, D. H., Smith, S. L., Hashimoto, K., Takemoto, T., Nonaka, M. I., Kimura, H., Flajnik, M. F., and Nonaka, M. (2003). Molecular cloning of C4 gene and identification of the class III complement region in the shark MHC. J Immunol 171,2461-6.
Terado, T., Smith, S. L., Nakanishi, T., Nonaka, M. I., Kimura, H., and Nonaka, M. (2001). Occurrence of structural specialization of the serine protease domain of complement factor B at the emergence of jawed vertebrates and adaptive immunity. Immunogenetics 53, 250-4.
Tom Tang, Y., Hu, T., Arterburn, M., Boyle, B., Bright, J. M., Palencia, S., Emtage, P. C., and Funk, W. D. (2005). The complete complement of C1q-domain-containing proteins in Homo sapiens. Genomics 86,100-11.
Wang, T., and Secombes, C. J. (2003). Complete sequencing and expression of three complement components, C1r, C4 and C1 inhibitor, of the classical activation pathway of the complement system in rainbow trout Oncorhynchus mykiss. Immunogenetics 55, 615-28.
Wang, Z., Zhang, S., Wang, G., and An, Y. (2008). Complement activity in the egg cytosol of zebrafish Danio rerio: evidence for the defense role of maternal complement components. PLoS ONE 3, el463.
Wright, J. F., Shulman, M. J., Isenman, D. E., and Painter, R. H. (1988). Cl binding by murine IgM. The effect of a Pro-to-Ser exchange at residue 436 of the mu-chain. J Biol Chem 263, 11221-6.
Yano,T.,and Nakao,M.(1994).Isolation of a carp complement protein homologous to mammalian factor D.Mol Immunol 31,337-42.
Yu,Y,Huang,H.,Wang,Y,Yu,Y,Yuan,S.,Huang,S.,Pan,M.,Feng,K.,and Xu,A.(2008).A novel C1q family member of amphioxus was revealed to have a partial function of vertebrate C1q molecule.J Immunol 181,7024-32.
Zarkadis,I.K.,Sarrias,M.R.,Sfyroera,G,Sunyer,J.O.,and Lambris,J.D.(2001).Cloning and structure of three rainbow trout C3 molecules:a plausible explanation for their functional diversity.Dev Comp Immunol 25,11-24.
王志平;张士璀;王光锋.(2008).鱼类补体系统成分及补体特异性和功能的研究进展.水生生物学报 32,760-769.
王兰兰;吴健民.(2007).“临床免疫学与检验.”人民卫生出版社,
白云;朱锡华.(1994).微量补体反应性溶血测定法.免疫学杂志10,127-129.
林学颜;张玲.(1999).“现代细胞与分子免疫学”科学出版社 北京
高晓明.(2006).“医学免疫学.”高等教育出版社,北京.
陈政良.(1997).C1qA链结构-功能研究进展.免疫学杂志13,128-130.
陈政良;谢佩蓉.(1996).补体经典途径非免疫性激活.国外医学免疫学分册 19,135.
Arlaud, G. J., Colomb, M. G., and Gagnon, J. (1987a). A functional model of the human C1 complex. Immunol. Today 8,106-111.
Arlaud, G. J., Gaboriaud, C., Thielens, N. M., Budayova-Spano, M., Rossi, V., and Fontecilla-Camps, J. C. (2002). Structural biology of the Cl complex of complement unveils the mechanisms of its activation and proteolytic activity. Mol Immunol 39, 383-94.
Bang, J. D., Kim, J. W., Lee, S. D., Park, S. I., Chun, S. G., S., J. C., and W., P. J. (1996a). Humoral immune response of flounder to Edwardsiella tarda: the presence of various sizes of immunoglobulins in flounder. Dis. quat. Organ. 26,197-203.
Bang, J. D., W., K. J., D., L. S., I., P. S., G., C. S., S., J. C., and W., P. J. (1996b). Humoral immune response of flounder to Edwardsiella tarda : the presence of various sizes of immunoglobulins in flounder. Dis. Aquat. Org. 26,197-203.
Bohlson, S. S., Fraser, D. A., and Tenner, A. J. (2007). Complement proteins C1q and MBL are pattern recognition molecules that signal immediate and long-term protective immune functions. Mol Immunol 44, 33-43.
Bork, P., and Bairoch, A. (1995). Extracellular modules. Trends Biochem. Sci. 20 (Suppl.), C03.
Boshra, H., Gelman, A. E., and Sunyer, J. O. (2004). Structural and functional characterization of complement C4 and C1s-like molecules in teleost fish: insights into the evolution of classical and alternative pathways. J Immunol 173,349-59.
Danilova, N., Bussmann, J., Jekosch, K., and Steiner, L. A. (2005). The immunoglobulin heavy-chain locus in zebrafish: identification and expression of a previously unknown isotype, immunoglobulin Z. Nat Immunol 6,295-302.
Dodds, A. W., and Matsushita, M. (2007). The phylogeny of the complement system and the origins of the classical pathway. Immunobiology 212,233-43.
Duncan, A. R., and Winter, G. (1988). The binding site for C1q on IgG. Nature 332, 738-740. Elcombe, B. M., Chang, R. J., Taves, C. J., and Winkelhake, J. L. (1985). Evolution of antibody structure and effector functions: comparative hemolytic activities of monomeric and tetrameric IgM from rainbow trout, Salmo gairdnerii. Comp Biochem Physiol B 80, 697-706.
Endo, Y., Nonaka, ML, Saiga, H., Kakinuma, Y., Matsushita, A., Takahashi, M., Matsushita, M., and Fujita, T. (2003). Origin of mannose-binding lectin-associated serine protease (MASP)-1 and MASP-3 involved in the lectin complement pathway traced back to the invertebrate, amphioxus. J Immunol 170,4701-7.
Endo, Y, Takahashi, M., and Fujita, T. (2006). Lectin complement system and pattern recognition. Immunobiology 211, 283-93.
Endo, Y., Takahashi, M., Nakao, M., Saiga, H., Sekine, H., Matsushita, M., Nonaka, M., and Fujita, T. (1998). Two lineages of mannose-binding lectin-associated serine protease (MASP) in vertebrates. J Immunol 161,4924-30.
Fairies, T. C., and Atkinson, J. P. (1991). Evolution of the complement system. Immunol Today 12, 295-300.
Flexner, S., and Noguchi, H. (1903). Snake venom in relation to haemolysis, bacteriolysis and toxicity. J.Exp.Med. 6,277-301.
Franchini, S., Zarkadis, I. K., Sfyroera, G., Sahu, A., Moore, W. T., Mastellos, D., LaPatra, S. E., and Lambris, J. D. (2001). Cloning and purification of the rainbow trout fifth component of complement (C5). Dev Comp Immunol 25,419-30.
Fujii, T., and Murakawa, S. (1981). Immunity in lamprey. III. Occurrence of the complement-like activity. Dev Comp Immunol 5,251-9.
Fujii, T., Nakamura, T., Sekizawa, A., and Tomonaga, S. (1992). Isolation and characterization of a protein from hagfish serum that is homologous to the third component of the mammalian complement system. J Immunol 148,117-23.
Fujita, T. (2002). Evolution of the lectin-complement pathway and its role in innate immunity. Nat Rev Immunol 2, 346-53.
Gasque, P. (2004). Complement: a unique innate immune sensor for danger signals. Mol Immunol 41, 1089-98.
Goh, C. S., Bogan, A. A., Joachimiak, M., Walther, D., and Cohen, F. E. (2000). Co-evolution of proteins with their interaction partners. J Mol Biol 299, 283-93.
Goh, C. S., and Cohen, F. E. (2002). Co-evolutionary analysis reveals insights into protein-protein interactions. J Mol Biol 324,177-92.
Hanley, P. J., Hook, J. W., Raftos, D. A., Gooley, A. A., Trent, R., and Raison, R. L. (1992). Hagfish humoral defense protein exhibits structural and functional homology with mammalian complement components. Proc Natl Acad Sci U S A 89, 7910-4.
Hansen, J. D., Landis, E. D., and Phillips, R. B. (2005). Discovery of a unique Ig heavy-chain isotype (IgT) in rainbow trout: Implications for a distinctive B cell developmental pathway in teleost fish. Proc Natl Acad Sci U S A 102,6919-24.
Holland, M. C., and Lambris, J. D. (2002). The complement system in teleosts. Fish Shellfish Immunol 12, 399-420.
Ishiguro, H., Kobayashi, K., Suzuki, M., Titani, K., Tomonaga, S., and Kurosawa, Y. (1992). Isolation of a hagfish gene that encodes a complement component. Embo J 11, 829-37.
Ji, X., Azumi, K., Sasaki, M., and Nonaka, M. (1997). Ancient origin of the complement lectin pathway revealed by molecular cloning of mannan binding protein-associated serine protease from a urochordate, the Japanese ascidian, Halocynthia roretzi. Proc Natl Acad Sci U S A 94, 6340-5.
Ji, X., Namikawa-Yamada, C., Nakanishi, M., Sasaki, M., and Nonaka, M. (2000). Molecular cloning of complement factor B from a solitary ascidian: unique combination of domains implicating ancient exon shufflings. Immunopharmacology 49,43.
Kaul, M., and Loos, M. (1993). The Fc-recognizing, collagen-like C1q molecule is a putative type II membrane protein of macrophages. Behring Inst Mitt, 171-9.
Kenjo, A., Takahashi, M., Matsushita, M., Endo, Y., Nakata, M., Mizuochi, T., and Fujita, T. (2001). Cloning and characterization of novel ficolins from the solitary ascidian, Halocynthia roretzi. J Biol Chem 276,19959-65.
Kishore, U., Gaboriaud, C., Waters, P., Shrive, A. K., Greenhough, T. J., Reid, K. B., Sim, R. B., and Arlaud, G. J. (2004). C1q and tumor necrosis factor superfamily: modularity and versatility. Trends Immunol 25, 551-61.
Kishore, U., Gupta, S. K., Perdikoulis, M. V., Kojouharova, M. S., Urban, B. C., and Reid, K. B. M. (2003). Modular organization of the carboxy-terminal, globular head region of human C1q A, B and C chains. J. Immunol 171, 812-820.
Kishore, U., Kojouharova, M. S., and Reid, K. B. (2002). Recent progress in the understanding of the structure-function relationships of the globular head regions of C1q. Immunobiology 205, 355-64.
Kishore, U., and Reid, K. B. (2000). C1q: structure, function, and receptors. Immunopharmacology 49, 159-70.
Kishore, U., and Reid, K. B. M. (1999). Modular organization of proteins containing C1q-like globular domains.. Immunopharmacol. 41,15-21.
Kocabas, A. M., Li, P., Cao, D., Karsi, A., He, C., Patterson, A., Ju, Z., Dunham, R. A., and Liu, Z. (2002). Expression profile of the channel catfish spleen: analysis of genes involved in immune functions. Mar Biotechnol (NY) 4, 526-36.
Koppenheffer, T. L., Spong, K. D., and Falvo, H. M. (1998). The complement system of the marsupial Monodelphis domestica. Dev Comp Immunol 22,231-7.
Leimeister, C., Steidl, C., Schumacher, N., Erhard, S., and Gessler, M. (2002). Developmental expression and biochemical characterization of Emu family members. Dev Biol 249, 204-18.
Lobb, C. J., and Olson, M. O. (1988). Immunoglobulin heavy H chain isotypes in a teleost fish. J Immunol 141,1236-45.
Maeurer, M. J., Trinder, P. K., Storkel, S., and Loos, M. (1993). C1q in autoimmune diseases: rheumatoid arthritis. Behring Inst Mitt, 262-78.
Magnadottir, B. (2000). The spontaneous haemolytic activity of cod serum: heat insensitivity and other characteristics. Fish Shellfish Immunol 10,731-5.
Magnadottir, B., Jonsdottir, H., Helgason, S., Bjornsson, B., Jorgensen, T. O., and Pilstrom, L. (1999a). Humoral immune parameters in Atlantic cod (Gadus morhua L.) I. The effects of environmental temperature. Comp Biochem Physiol B Biochem Mol Biol 122,173-80.
Magnadottir, B., Jonsdottir, H., Helgason, S., Bjornsson, B., Jorgensen, T. O., and Pilstrom, L. (1999b). Humoral immune parameters in Atlantic cod (Gadus morhua L.) II. The effects of size and gender under different environmental conditions. Comp Biochem Physiol B Biochem Mol Biol 122,181-8.
Magnadottir, B., Jonsdottir, H., Helgason, S., Bjornsson, B., Solem, S. T., and Pilstrom, L. (2001). Immune parameters of immunised cod (Gadus morhua L.). Fish Shellfish Immunol 11,75-89.
Marshall, H. T. (1904). Studies in haemolysis with special reference to the properties of blood and body fluids of Human beings. J. Exp. Med. 6, 309-332.
Matsushita, M., Matsushita, A., Endo, Y., Nakata, M., Kojima, N., Mizuochi, T., and Fujita, T. (2004). Origin of the classical complement pathway: Lamprey orthologue of mammalian C1q acts as a lectin. Proc Natl Acad Sci U S A 101,10127-31.
McNabb, T., Koh, T. Y., Dorrington, K. J., and Painter, R. H. (1976). Structure and function of immunoglobulin domains. V. Binding, University of immunoglobulin G and fragments to placental membrane preparations. J Immunol 117,882-8.
Mei, J., and Gui, J. (2008). Bioinformatic identification of genes encoding C1q-domain-containing proteins in zebrafish. J Genet Genomics 35, 17-24.
Nakao, M., Fushitani, Y., Fujiki, K., Nonaka, M., and Yano, T. (1998). Two diverged complement factor B/C2-like cDNA sequences from a teleost, the common carp (Cyprinus carpio). J Immunol 161,4811-8.
Nakao, M., Mutsuro, J., Obo, R., Fujiki, K., Nonaka, M., and Yano, T. (2000). Molecular cloning and protein analysis of divergent forms of the complement component C3 from a bony fish, the common carp (Cyprinus carpio): presence of variants lacking the catalytic histidine. Eur J Immunol 30, 858-66.
Nakao, M., and Yano, T. (1998). Structural and functional identification of complement components of the bony fish, carp (Cyprinus carpio). Immunol Rev 166,27-38.
Nonaka, M. (2001). Evolution of the complement system. Curr Opin Immunol 13, 69-73.
Nonaka, M., Azumi, K., Ji, X., Namikawa-Yamada, C., Sasaki, M., Saiga, H., Dodds, A. W., Sekine, H., Homma, M. K., Matsushita, M., Endo, Y., and Fujita, T. (1999). Opsonic complement component C3 in the solitary ascidian, Halocynthia roretzi. J Immunol 162,387-91.
Nonaka, M., Fujii, T., Kaidoh, T., Natsuume-Sakai, S., Nonaka, M., Yamaguchi, N., and Takahashi, M. (1984). Purification of a lamprey complement protein homologous to the third component of the mammalian complement system. J Immunol 133,3242-9.
Nonaka, M., Kuroda, N., Naruse, K., and Shima, A. (1998). Molecular genetics of the complement C3 convertases in lower vertebrates. Immunol Rev 166, 59-65.
Nonaka, M., Natsuume-Sakai, S., and Takahashi, M. (1981a). The complement system in rainbow trout (Salmo gairdneri). II. Purification and characterization of the fifth component (C5). J Immunol 126,1495-8.
Nonaka, M., Nonaka, M., Irie, M., Tanabe, K., Kaidoh, T., Natsuume-Sakai, S., and Takahashi, M. (1985). Identification and characterization of a variant of the third component of complement (C3) in rainbow trout (Salmo gairdneri) serum. J Biol Chem 260, 809-15.
Nonaka, M., and Smith, S. L. (2000). Complement system of bony and cartilaginous fish. Fish Shellfish Immunol 10, 215-28.
Nonaka, M., and Takahashi, M. (1992). Complete complementary DNA sequence of the third component of complement of lamprey. Implication for the evolution of thioester containing proteins. J Immunol 148, 3290-5.
Nonaka, M., Takahashi, M., and Sasaki, M. (1994). Molecular cloning of a lamprey homologue of the mammalian MHC class III gene, complement factor B. J Immunol 152,2263-9.
Nonaka, M., Yamaguchi, N., Natsuume-Sakai, S., and Takahashi, M. (1981b). The complement system of rainbow trout (Salmo gairdneri). I. Identification of the serum lytic system homologous to mammalian complement. J Immunol 126,1489-94.
Nonaka, M., and Yoshizaki, F. (2004). Evolution of the complement system. Mol Immunol 40, 897-902.
Reid, K. B. M., and Porter, R. R. (1976). Subunit composition and structure of subcomponent C1q of the first component of human complement. Biochem. J. 155,19-23.
Rombout, J. H., Taverne, N., van de Kamp, M., and Taverne-Thiele, A. J. (1993). Differences in mucus and serum immunoglobulin of carp (Cyprinus carpio L.). Dev Comp Immunol 17, 309-17.
Savan, R., Aman, A., Nakao, M., Watanuki, H., and Sakai, M. (2005a). Discovery of a novel immunoglobulin heavy chain gene chimera from common carp (Cyprinus carpio L.). Immunogenetics 57, 458-63.
Savan, R., Aman, A., Sato, K., Yamaguchi, R., and Sakai, M. (2005b). Discovery of a new class of immunoglobulin heavy chain from fugu. Eur J Immunol 35,3320-31.
Sekine, H., Kenjo, A., Azumi, K., Ohi, G., Takahashi, M., Kasukawa, R., Ichikawa, N., Nakata, M., Mizuochi, T., Matsushita, M., Endo, Y., and Fujita, T. (2001). An ancient lectin-dependent complement system in an ascidian: novel lectin isolated from the plasma of the solitary ascidian, Halocynthia roretzi. J Immunol 167,4504-10.
Shulman, M. J., Collins, C., Pennell, N., and Hozumi, N. (1987). Complement activation by IgM: evidence for the importance of the third constant domain of the mu heavy chain. Eur J Immunol 17, 549-54.
Smith, L. C., Azumi, K., and Nonaka, M. (1999). Complement systems in invertebrates. The ancient alternative and lectin pathways. Immunopharmacology 42,107-20.
Smith, L. C., Chang, L., Britten, R. J., and Davidson, E. H. (1996). Sea urchin genes expressed in activated coelomocytes are identified by expressed sequence tags. Complement homologues and other putative immune response genes suggest immune system homology within the deuterostomes. J Immunol 156, 593-602.
Smith, L. C., Shih, C. S., and Dachenhausen, S. G. (1998). Coelomocytes express SpBf, a homologue of factor B, the second component in the sea urchin complement system. J Immunol 161, 6784-93.
Smith, S. L. (1998). Shark complement: an assessment. Immunol Rev 166, 67-78.
Sunyer JO, and JD, L. (1999). "Encyclopedia of life sciences." Macmillan References Limited,
Sunyer, J. O., and Lambris, J. D. (1998). Evolution and diversity of the complement system of poikilothermic vertebrates. Immunol Rev 166,39-57.
Sunyer, J. O., Tort, L., and Lambris, J. D. (1997). Diversity of the third form of complement, C3, in fish: functional characterization of five forms of C3 in the diploid fish Sparus aurata. Biochem J 326(Pt 3), 877-81.
Sunyer, J. O., Zarkadis, I., Sarrias, M. R., Hansen, J. D., and Lambris, J. D. (1998). Cloning, structure, and function of two rainbow trout Bf molecules. J Immunol 161,4106-14.
Sunyer, J. O., Zarkadis, I. K., Sahu, A., and Lambris, J. D. (1996). Multiple forms of complement C3 in trout that differ in binding to complement activators. Proc Natl Acad Sci U S A 93, 8546-51.
Suzuki, M. M., Satoh, N., and Nonaka, M. (2002). C6-like and C3-like molecules from the cephalochordate, amphioxus, suggest a cytolytic complement system in invertebrates. J Mol Evol 54,671-9.
Terado, T., Nonaka, M. I., Nonaka, M., and Kimura, H. (2002). Conservation of the modular structure of complement factor I through vertebrate evolution. Dev Comp Immunol 26,403-13.
Terado, T., Okamura, K., Ohta, Y., Shin, D. H., Smith, S. L., Hashimoto, K., Takemoto, T., Nonaka, M. I., Kimura, H., Flajnik, M. F., and Nonaka, M. (2003). Molecular cloning of C4 gene and identification of the class III complement region in the shark MHC. J Immunol 171,2461-6.
Terado, T., Smith, S. L., Nakanishi, T., Nonaka, M. I., Kimura, H., and Nonaka, M. (2001). Occurrence of structural specialization of the serine protease domain of complement factor B at the emergence of jawed vertebrates and adaptive immunity. Immunogenetics 53, 250-4.
Tom Tang, Y., Hu, T., Arterburn, M., Boyle, B., Bright, J. M., Palencia, S., Emtage, P. C., and Funk, W. D. (2005). The complete complement of C1q-domain-containing proteins in Homo sapiens. Genomics 86,100-11.
Wang, T., and Secombes, C. J. (2003). Complete sequencing and expression of three complement components, C1r, C4 and C1 inhibitor, of the classical activation pathway of the complement system in rainbow trout Oncorhynchus mykiss. Immunogenetics 55, 615-28.
Wang, Z., Zhang, S., Wang, G., and An, Y. (2008). Complement activity in the egg cytosol of zebrafish Danio rerio: evidence for the defense role of maternal complement components. PLoS ONE 3, el463.
Wright, J. F., Shulman, M. J., Isenman, D. E., and Painter, R. H. (1988). Cl binding by murine IgM. The effect of a Pro-to-Ser exchange at residue 436 of the mu-chain. J Biol Chem 263, 11221-6.
Yano,T.,and Nakao,M.(1994).Isolation of a carp complement protein homologous to mammalian factor D.Mol Immunol 31,337-42.
Yu,Y,Huang,H.,Wang,Y,Yu,Y,Yuan,S.,Huang,S.,Pan,M.,Feng,K.,and Xu,A.(2008).A novel C1q family member of amphioxus was revealed to have a partial function of vertebrate C1q molecule.J Immunol 181,7024-32.
Zarkadis,I.K.,Sarrias,M.R.,Sfyroera,G,Sunyer,J.O.,and Lambris,J.D.(2001).Cloning and structure of three rainbow trout C3 molecules:a plausible explanation for their functional diversity.Dev Comp Immunol 25,11-24.
王志平;张士璀;王光锋.(2008).鱼类补体系统成分及补体特异性和功能的研究进展.水生生物学报 32,760-769.
王兰兰;吴健民.(2007).“临床免疫学与检验.”人民卫生出版社,
白云;朱锡华.(1994).微量补体反应性溶血测定法.免疫学杂志10,127-129.
林学颜;张玲.(1999).“现代细胞与分子免疫学”科学出版社 北京
高晓明.(2006).“医学免疫学.”高等教育出版社,北京.
陈政良.(1997).C1qA链结构-功能研究进展.免疫学杂志13,128-130.
陈政良;谢佩蓉.(1996).补体经典途径非免疫性激活.国外医学免疫学分册 19,135.