儿童支气管肺炎血小板计数及相关炎症因子变化的研究
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摘要
目的1.探讨外周血血小板计数是否可以作为早期判断儿童肺炎病情轻重的指标。2.探讨血小板活化及其炎症因子在儿童喘息性肺炎中的作用。
     方法1.对102例支气管肺炎伴有血小板增多的患儿(A组)与107例支气管肺炎血小板计数正常的患儿(B组)的临床特点、实验室指标(肝功能、心肌酶谱、白细胞计数、C反应蛋白)、潮气通气肺功能、免疫功能、血小板膜表面CD62P以及血浆肿瘤坏死因子-α(TNF-α)和白细胞介素(IL-6)浓度等进行比较。2.测定21例喘息性肺炎儿童(喘息组)、12例非喘息性肺炎儿童(非喘息组)组和10例健康儿童(健康组)血小板膜表面CD62P的表达、血浆P-选择素和转化生长因子-β(TGF-β)浓度。将三组儿童的富血小板血浆用胶原进行刺激,测定刺激后的血浆TGF-β和P选择素的含量。
     结果1.A组患儿临床症状比B组患儿重,表现为A组发生呼吸困难和喘息的比例高,住院时间长,白细胞计数高,代表小气道阻塞的肺功能指标呼气达峰时间(tPTEF)、达峰时间比(呼气达峰时间/呼气时间、tPTEF/tE)、剩余25%潮气量时的呼气流速(TEF25)、剩余25%潮气量时的呼气流速/呼气峰流速(TEF25/PTEF%)降低,IgA、IgG水平降低, CD3+细胞比例下降,两组相比有显著性差异(P<0.05)。A组患儿CD3-CD19+和CD19+CD23+细胞比例增高,血小板膜表面CD62P表达增高,血浆TNF-α、IL-6增高,与B组比较差异有显著性(P<0.05)。肺炎伴血小板增多大都发生在小年龄组(P<0.05)。2.喘息组患儿的CD62P比健康组高,两组比较差异有显著性(P<0.05)。三组患儿的富血小板血浆给予胶原刺激,刺激后三组血浆P-选择素和TGF-β浓度均比刺激前增加,有显著性差异(P<0.05)。刺激后喘息组血浆P选择素浓度比非喘息组和健康组高,均有显著性差异(P<0.05)。刺激后喘息组TGF-β浓度最高,非喘息组其次,健康组最低,三组之间两两比较,均有显著性差异(P<0.05)。
     结论1.外周血血小板计数可作为评判肺炎轻重并指导治疗的实用指标,年龄越小,实用价值越大。
     2.喘息性肺炎患儿存在血小板活化增强,潜在的血小板内炎症因子高表达。
     3.血小板及其炎症因子在喘息性肺炎中起促进炎症反应作用。
Objective:1. To analyze the clinical significance and prognostic value of platelet count in pneumonia in pediatric patients . 2.To investigate the roles of platelets’activation and platelet released inflammatory factor in pneumonia children with wheezing.
     Methods:1.The study included 102 patients with thrombocytosis in pneumonia (group A)and 107 patients with normal platelet counts in pneumonia(group B).We compared clinical data, laboratory data(Hepatic function, cardiac enzyme, and C-reactive protein),tidal breathing lung function, immunologic function ,the expression of CD62P on platelets and plasma tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6) concentrations between the two groups. 2.We determined the expression of CD62P on platelets and plasma transforming growth factor-βand P-selectin levels among children in pneumonia with wheezing(wheezing group) , without wheezing(no wheezing group) and normal subjects(normal group).We isolated platelet-rich plasma from these children’s blood . Then stimulated the platelet-rich plasma with collagen for 30 minutes . Plasma transforming growth factor-β(TGF-β) and P-selectin levels were measured after stimulation.
     Results:1. Compared with group B, group A had a more severe clinical conditions:presence higher percentage of dyspnea and wheezing and longer hospitalization, white blood count increased ,lung faction parameter including tPTEF、tPTEF/tE、TEF25 and TEF25/PTEF %decreased ,the levels of IgA、IgG in serum declined,the ratio of CD3+leukomonocyte’s declined,CD3-CD19+ and CD19+CD23+ leukomonocyte percentage increased, the expression of CD62P on platelets and plasma TNF-αand IL-6 concentrations raised .The difference between the two groups was statistically significant (P<0.05). Patientes in group A were younger than patients in group B, The difference between the two groups was statistically significant (P<0.05).
     2.The expression of CD62P on platelet in wheezing group was higher than that of normal group, the difference between the two groups was statistically significant (P<0.05). After stimulated the platelet-rich plasma with collagen for 30 minutes , plasma transforming growth factor-β(TGF-β)and P-selectin levels were higher than before stimulation, the difference was statistically significant (P<0.05). The plasma P-selectin concentration of wheezing group after stimulation is higher than that of no wheezing group and normal group,and the difference between them was statistically significant (P<0.05). After stimulation , the plasma TGF-βconcentration of wheezing group after stimulation is higher than that of no wheezing group and normal group, while the plasma TGF-βconcentration of no wheezing group is higher than that of normal group, the difference between them were statistically significant (P<0.05).
     Conclusions:The severity of pneumonia in chidren is associated with platelet count . Platelet count is a useful clinical marker in judging the severity of pneumonia and guiding therapy, especially in low ages such as infants. The platelet of patients with wheezing had enhanced activity and had much more inflammatory factors . After stimulation,the platelet of patients with wheezing actived and released much more inflammatory factors such as TGF-βand P-selectin and promoted inflammation and induced wheezing .
引文
1. Pechere JC.Community acquired pneumonia in chidren[M].West Sussex:Cambridge Medical Publishing House,1995:29-34.
    2. 方怡,冉丕鑫.重症社区获得性肺炎炎性机制研究进展[J].国外医学呼吸系统分册,2005,25(1):23.
    3. 陈业民,黄文杰,李胜利,等.重症肺炎大鼠干扰素-γ、白细胞介素-6和肿瘤坏死因子-α含量变化[J].中国病理生理杂志,2007,23(3):492—494.
    4. 余峰,崔敏娴,姚冬莉,等.儿童重症肺炎血清致炎性细胞因子变化及意义探讨[J].医学研究杂志,2007,36(2):74-76.
    5. Vasiliki Vlacha,Gavriela Feketea.Thrombocytosis in pediatric patients is associated with severe lower respiratory tract inflammation[J].Archives of Medical Research,2006,37:755-759.
    6.林娜,黄月艳,急性感染患儿危重病例评分与血小板数关系的探讨[J].右江民族医学院学报,2003(3):364-366.
    7. ünsal E, Aksaray S, K?ksal D, et al. Potential role of interleukin 6 in reactive thrombocytosis and acute phase response in pulmonary tuberculosis[J].Postgrad Med J,2005,81:604-607.
    8. Marc A. Brockmann, Alf Giese, Kathrin Mueller,et al. Preoperative thrombocytosis predicts poor survival in patients with glioblastoma [J]. Neuro-Oncology. 2007,(9): 335–342.
    9. Auraham H,Ellis MH,Jhun BH et a1.Tyrosine kinaese in megakaryocytopoiese [J].Stem Cell,1995,(13):380—387.
    10. Valade N., Decailliot F., Re′bufat Y.,et al. Thrombocytosis after trauma: incidence, aetiology, and clinical significance[J]. British Journal of Anaesthesia 2005,94 (1): 18–23.
    11. 庞戈红,方美云. 儿科重症监护病区中继发性血小板增多症 52例临床分析[J]. 实用医学杂志2005,21,(19)2185-2186.
    12. Ishiguro K,Nakahata T,Matsubara,et al.Age-related changes in thrombopoietin in children:reference interval for serum thrombopoietin levels[J].Br J Haematoi,1999,106:884-888.
    13. 黄小霏, 陈昭仪,范联.小儿重症肺炎血小板参数的动态变化分析[J].岭南急诊医学杂志2006,11(4):269-270.
    14. Slavica D,Miljenko R,Kornelija K,et al.Thrombopoietin and interleukin-6 in children with pneumonia-associated thrombocytosis[J].Archieves of Medical Research,2005,36:124-128.
    15. Cutrera R,Filtehev S I,Merolla R,et a1.Analysis of expiratory pattern for monitoring bronchial obstruction in school-age children[J].Pediatr Pulmonol,1991,10(1):6.
    16. Bradding P,Roberts JA,Britten KM,et al.Interleukin-4,-5,-6 and tumour necrosis factor-alpha in normal and asthmatic airways:evidence for human mast cell as a source of these cytokines[J].AmJ.Respir.Cell Mol Bid,1994,10:471-480.
    18. OkamoteH,YamamuraM,MoritaY,et al.The synovial expression and serum levels of interleukin-6,interleukin-11,leukemia inhibitory factortor,and oncostatin in rheumatoid arthritis[J].Arthritis Rheum,1997,40(6):1096-1105.
    19.Ksontini R,Mackay SL,Moldawer LL. Revisiting the role of tumor necrosis factor alpha and the response to surgical injury and inflammation[J].Arch Surg.1998,133:558-567.
    20. Mathy NL, Mathy JP, Lee RP, et a1. Pathological and immunological changes after challenge infection with Pasteurella multocida in naive and immunized calyes[J]. Vet Immunol Immunopathol.2002,85:179—188.
    21.赵玉玲,冯卫东,鲍立春.肺内细菌感染患者血清及肺泡灌洗液白介素-8、白介素-6、肿瘤坏死因子α检测及意义[J].中华临床医学研究杂志,2005,11,(3)601-602.
    22. 施焕忠,林江涛.肺脏免疫学及免疫相关性疾病[M].第1版.北京:人民卫生出版社,2006:236-256.
    23. 胡 亚 美 , 江 载 芳 . 诸 福 棠 实 用 儿 科 学 [M]. 第 7 版 . 北 京 : 人 民 卫 生 出 版社,2002:1174-1185.
    24. 张明智,王立波,陈超. 树突状细胞在儿童重症肺炎发病机制中的作用[J]. 中华儿科杂志,2005,43(6)410-413.
    25. 栾杰,尹立岩,马 燕,李东. 支原体肺炎肺外损伤患儿T细胞亚群、IFN-γ、TNF-α的变化及意义[J].山东医药2006年第46卷第22期:3-4.
    26. Blann AD,Lip GY.Hypothesis.Is soluble P-selectin a new marker of platelet activation? [J].Atheroscler0sis,1997,128(2):135-138.
    27. Schober A,Manka D,Hundelshausen P,et al.Deposition of platelet RANTES triggering monocyte recruitment requires P-selectin and is involved in neointima formation after arterial injury[J].Circulation,2002,106(12):1523-1529.
    28. Frenette PS,Mayadas TN,Rayburn H,er al.Susceptibility to infection and altered hematopoiesis in mice deficient in both P-and E-selectins[J].Cell,1996,84(4):563-574.
    29. Dang B,Wiehler S,Patel KD.Increased PSGL-1 expression on granulocytes from allergic-asthmatic subjects results in enhanced leukocyte recruitment under flow conditions[J].J Leukoc BiolL,2002,72(4):702-710.
    30. Kaser A,Brandacher G,Steurer W,et al.Interleukin-6 stimulates thrombopoiesis through thrombopoietin:role in inflammatory thrombocytosis[J].Blood,2001;98:2720-2725.
    31. Hsu Hc,Tsai WH,Jiang Ml,et al.Circulating levels of thrombopoietic and inflammatory cytokines in patients with clonal and reactive thrombocytosis[J].J Lab Clin Med ,1999,134(4):392-397.
    32. Fernandez-Serrano S,Dorca J,Coromines M,et al.Molecular inflammatory responses measured in blood of patients with severe community-acquired pneumonia[J].Clin Diagn Lab Immunol 2003,10(5):813-820.
    33. Greene C,Lowe G,Taggart C,et al.Tumor necrosis factor-alpha-converting enzyme:its role in community-acquired pneumoniae[J].J Infect Dis 2002,186(12):1790-1796.
    34. Dan K,Gomi S,Inokuchi K.Effects of interleukin-1 and tumor necrosis factor on megakaryocytopoiesis:mechanism of reactive thrombocytosis[J].Acta Haematol 1995,93(24):67-72.
    35. Klinger MH,Jelkmann W.Role of blood platelets in infection and inflammation[J].J Interferon Cytokine Res 2002,22(9):913-922.
    36. 郑美琴,楼永良,王怡.血小板活化在儿童呼吸道感染发病中的意义[J].温州医学院学报,2003,33(4):250-252.
    37. Martin TF,Slater DN,Trowbridge EA.Platelet production in the lungs[J]. In: Schmitz-Schuman M,Menz G,page CP,eds.PAF,platelets,and asthma:Agents and Actions (suppl21).Basal:Brikhauser Verlag,1987:37-57.
    1. 董宗祈.支气管哮喘的肾上腺受体及其药物治疗[J].中华儿科杂志,2001;39(6):373.
    2. 胡 亚 美 , 江 载 芳 . 诸 福 棠 实 用 儿 科 学 [M]. 第 7 版 . 北 京 : 人 民 卫 生 出 版社,2002:1174-1185.
    3. 吕婕,范亚可,董晓燕,等.伴喘息症状的肺炎患儿临床及病原学研究[J].中国当代儿科杂志,2005,7(3):259-260.
    4. Martinez FD,Wright AL,Taussing LM,et al.Asthma and wheezing in the first years of life[J].New EnglJ.Med,1995,332-333.
    5. 黄英,沈锦,陈坤华,等.喘息性疾病 T、B 细胞功能和 IgE 水平相互关系探讨[J].上海免疫学杂志,1994,14(1):23-27.
    6. 中华医学会儿科学分会呼吸学组,中华医学会《中华儿科杂志》编辑委员会. 儿童支气管哮喘防治常规(试行) [J].中华儿科杂志,2004,42 (2):100-106.
    7. Weyrich AS,Lindemann S,Zimmerman GA.The evoling role of platelets in inflammation[J].J.Thromb Haemost,2003(1):1897-1905.
    8. Falco A,Romano M,Lapichinol,et al.Increased soluble CD40 ligand levels in cystic fribrosis[J].J Thromb Haemost,2004,(2):557-560.
    9. Blann AP,Lip Y.Hypothesis:Is soluble P-selectin a new marker of platelet activiation? [J].Atherosclerosis,1997,128(2):135-138.
    10. Schober A,Manka D,Hundelshausen P.et al.Deposition of platelet RANTES triggering monocyto recruitment requires P-selectin and is involved in neointuma formation after arterial injury[J].Circulation,2002,106(12):1523-1529.
    11. Sullion PJ,Jatar ZH.Harbison PL,et al.Platelet dynamics following allergen chanllenge in allergic asthmatics[J].Respiration,2006,67(5):514-517.
    12. Dang B,Wiehler S,Patel KD.Increased PSGL-1 expression on granulocytes from allergic-asthmatic subjects results in enhanced leukocyte recruitment under flow conditions[J].J.Leukoc Biol,2002,72(4):702-710.
    13. 衡伟,王光杰,王兆钺,等.血小板活化在哮喘发病中的意义[J].中华结核与呼吸杂志,2000, 2 3(6):343-346.
    14. 雷伟,黄建安,陈延斌,等.联合吸入沙美特罗/丙酸氟替卡松对哮喘患者血小板膜蛋白分子表达的影响[J].临床荟萃,2005,20(17):974-976.
    15. 雷 伟,黄建安, 於葛华,等. 血小板源性 CD40L、CD62P 在哮喘患者外周血中的表达及其临床意义[J]. 国际呼吸杂志,2006,26 (1):8-12.
    16. De Sanctis GT,Wolyniec WW, Green FEY,et al.Reduction of allergic airway responses in P-selectin-deficient mice[J]. J Appl Physiol,1997:83:681-687.
    17. Pitchford SC,Riffo-Vasquez Y,Sousa A,et al.Platelets are necessary for airway remodeling in a murine model of chronic allergic inflammation[J]. Blood, 2004, 103:639-647.
    18.Pitchford SC,Momi S,Giannini S,et al.Platelet P-selectin is required for pulmonary eosinophil and lymphocyte recruitment in a murine model of allergic inflammation[J]. Blood,2005,105:2074-2081.
    19.Laurien HU.Dianne PHJ,Corneli WVA,et al.Platelet promote eosinophil adhesion of patients with asthma to endothelium under flow conditions[J].Am.J.Cell Mol. Biol, 2003,28:512-519.
    20.Kowal K, Pampuch A, Kowal-Bielecka O , et al.Platelet activation in allergic asthma patients during allergen challenge with dermatophagoides pteronyssinus[J].Clin Exp Allergy,2006 ,36(4):426-32.
    21.Chen G.Grotendorst G,Eicholtz,et al.GM-CSF increases airway smooth muscle cell connective tissue expression by inducing TGF-βreceptors[J].Am.J.Physiol Lung Cell Mol Physiol,2002,284(3):548-556.
    22.Duvernelle C,Freund ,Frossard,et al.Transforming growth factor beta and its role in asthma [J].Pulm Phamacol Ther,2003,16(4):181-196.
    23. Amanda L.T, Joanne P., Alan K,er al. Tryptase activates TGFb in human airway smooth muscle cells via direct proteolysis[J].Bithem.Biophy.Res. Commun.2008,doi (10):1016-1019.
    24. Bartram U,Speer CP.The role of transforming growth factor βin lung development and disease[J].Chest,2004,125(2):754-765.
    25. Nakao A.Is TGF-beta1 the key to suppression of human asthma? [J].Trends Immunol ,2001,22(3):115-118.
    26. Scherf W,Burdach S,Hansen G.Reduced expression of transforming growth factor beta1 exacerbates pathology in an experimental asthma model[J].EurJ Immumol,2005,35(1):198-206.
    27. Curotto DL.Lafaille MA,Lafaille JJ.The role of regulatory Tcells in allergy[J].Springer Semin Immunopathol,2004,25(3-4):295-310.
    28. Alam R,Forsythe P.Stafford S,et al.Transforming growth facor-βabrogates the effects of hamatopoietins in eosinophils and induces their apoptosis[J].J Exp Med, 1994, 179(3):1041-1045.
    29. 郁志伟.转化生长因子-β 与支气管哮喘[J].国际儿科杂志.2006,33(2):90-92.
    30. 李善玉,赵凯姝,李波,等.哮喘儿童血清白细胞介素 4、 转化生长因子-β1 和 IgE 水平的变化及临床意义[J].吉林大学学报《医学版》,2005,31(4):602-604.
    31. Adam M.G, Kelley B,Limei Z,et al.Transforming growth factor-β induces airway smooth muscle hypertrophy [J].Am J Respir Cell Mol Biol,2006,34:247-254.
    32. Alfors T,Mark H,Tim O,et al.Expression and activiation of TGF-β in acute allergen -induced remodeling in asthma[J].Thorox,2007,62:307-313.
    33. 徐毛冶,黄茂,,转化生长因子 β1 与支气管哮喘的关系[J].国外医学呼吸系统分册.2005,25(4):275-276.
    34. McMillan SJ,Lloyd CM,Prolonged allergen challenge in mice leads to persistene airway remodeling[J].Clin.exp Allergy,2004,34(3):497-507.
    35. Minshall EM,Leung DYM,Martin RJ,et al.Eosipophil-assiociated TGF-β1 mRNA expression and airwalls fibrosis in bronchal asthma[J].Am J Pespir Cell Mol Biol,1997,17(3):326-333.
    36. McMillan SJ,Xanthou G, Lloyd CM.Manipulation of allergen-induced airway remodeling by treatment with anti-TGFbeta antibody:effect on the smad signaling pathway[J].J Immunol,2005,174:5774-80.
    37. Mak JW,Rousell J,Haddad EB,et al.Transforming growth factor-β1 inhibits β2-adrenoceptor gene transcription[J].Naunyn Schmiedeberg’s Arch Pharmacol,2002,362:520-525.
    38. 范大平,张一梅,霍建民.支气管哮喘患者血及诱导痰中转化生长因子-β1 表达的研究[J].中国急救医学杂志,2006,26(10):663-666.
    39. Hara K,Hasegava t,Ooi H,et al.Inhibitory role of eosinophils cell surface plasmin generation by bronchial epithelial cells:inhibitory effects of transforming growth factorβ1[J] .Lung,2001,179:9-20.
    40. Martin TF,Slater DN,Trowbridge EA.Platelet production in the lungs[J]. In: Schmitz -Schuman M,Menz G,page CP,eds.PAF,platelets,and asthma:AgentsandActions (suppl21).Basal:BrikhauserVerlag,1987:37-5 .
    41. Metzger WJ,Sjoerdsma K,Richerson HB.et al.Platelets in bronchoalveolar lavage from asthmastic patients and allergic rabbits with allergen-induced late phase reaponses[J].In: In:Schmitz-Schuman M,Menz G,page CP,eds.PAF,platelets,and asthma:Agents and Actions(suppl21).Basal:Brikhauser Verlag,1987:151-59.
    42. Moritani C.Ishioka S.Haruta Y.et al.Activation of platelets in bronchial asthma[J]. Chest,1998:113:452-458.
    1. Blann AD, Lip GY. Hypothesis:Is soluble P-selection a new marker of platelet activation?[J].Atherosclerosis,19 97,128(2):135-138.
    2. 衡伟,王光杰,王兆钺,等.血小板活化在哮喘发病中的意[J]义.中华结核与呼吸杂志,2000, 23(6):343-346,
    3. Schober A, Manka D, Hundelshausen P, et al. Deposition of platelet RANTES triggering monocyte recruitment require sP-selectin and is involved in neointima formationa fterar terialin jury[J].C irculation,20 02,106(12):1523-1529.
    4. Frenete PS, Mayadas TN, Rayburn H, et al. Susceptibility to infection and altered hematopoiesis in mice deficientin both P–and E -selectins[J].Cell,1996,84 (4):563-574.
    5. BlanksJE ,MollnT ,Eytner R ,et al .Stimulation of P -selecting lycoprotein ligand-1 on mouse neutrophils activates beta2 –integrin mediated cell attachment to ICAM-l[J].Eur Iimmunol,1998,2 8(2):433-443.
    6. Mcever RP, Cummings RD. Role of PSGL-1 binding to selectins in leukocyterec ruitment[J].J Clin Invest,19 97,100(3):485-491.
    7. Hidari KI,Weyrich A S,Zimmerman GA,et al .Engagement of P–selectin glycoprotein ligand-I enhances tyrosine phosphorylation and activates mitogen-activated proteinkinases in human neutrophils[J].J Biol Chem,19 97,27 2(45):28750-28756.
    8. Henricks PA, Nijkamp FP. Reactive oxygen species as mediators in asthma[J]. Pulm Pharmacol Ther,2001,14 (6):409-421.
    9. SzalaiC ,Kozma GT,Nagy A ,et al .Polymorphism in the gene regulatory region of MCP-1 is associated with asthma susceptibility and severity. [J]J Allergy Clin Innmunol.2001, 108(3):375-381.
    10. Sullivan PJ, Jafar ZH, Harbinson PL, et al. Platelet dynamics following allergen challenge in allergic asthmatics[J].Respiration,20 00,67(5):514-517.
    11. Dang B, Wiehler S, Patel KD. Increased PSGL-l expression on granulocytes from allergic-asthmatic subjects results in enhanced leukocyte recruitment under flow conditions[J].J Leukoc Biol,20 02,72(4):702-710.
    12. Fijnheer R, Frijns CJ, Korteweg J, et al. The origin of P-selectin as a circulating plasma protein[J].Thromb Haemost,1997,77 (6):1081-1085.
    13.HennV ,Sl upskyJ R,G rafeM ,et al .CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells[J].Nature,19 98,39 1(6667):591-594
    14. Henn V, Steinbach S, Buchner K, et al. The inflammatory action of CD40 ligand(CD154) expressed on activated human platelets is temporally limited by coexpressed CD40[J] .Blood,2001,98 (4):1047-1054.
    15. Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis[J]. Circulation, 2002,105(9):1135-1143.
    16. Garlichs CD, John S, Schmeiber A, et al. Upregulation of CD40 and CD40 ligand (CD154)in patients with moderate hypercholesterolemia[J].Circulation,2001,104 (20): 2395-2400.
    17.Silvio D ,Carol M ,Andreas S ,et al .Platelets trigger a CD40-dependent inflammatory response in the microvasculature of inflammatory bowel disease patients[J]. Gastroenterology,20 03,12 4(5):1249-1264.
    18. Moritani C, Ishioka S, Haruta Y,et al. Activation of platelets in bronchial asthma[J].Chest,1998,113(2):452-458.
    19. Andre P, Nannizzi-Alaimo L, Prasad S, et al. Platelet-derived CD40L: the switch-hiting player of cardiovascular disease[J].Circulation,20 02,106(8):896-899.
    21.Inwald DP, Mcdowall A, Peters MJ, et al. CD40 is constitutively expressed on platelets and provides a novel mechanism for platelet activation[J]. Cire Res, 2003,92(9):1041一1048.
    21 Herd CP, Page CP. Pulmonary cells in health and disease: platelets[J]. Eur Respir rJ, 1994,7( 6):1145-1160.
    22.Freedman JE.CD40-CD40L and function:beyond haemostasis[J].Circ Res,20 03,92(9):944-946.
    23. Morris AE, Remmele RJ, Klinke R, et al. Incorporation of an isoleucine enhances the biological of soluble CD40L (CD154) [J].J Biolzipper Chem, motif 1999,274(1):418-423.
    24.Kushimoto S ,Okajima K ,Uchiba M ,et al.Pulmonary vascular injury induced by hemorrhagic shock is mediated by P-selectin in rats[J].T hromb Res,1996,82 (l):97-106.
    25 .Mehiop PD,Rijn van de M ,Brewer JP,et al .CD40L,but not CD40,is required for allergen-induced bronchial hyperresponsiveness in mice[J].Am J Respir Cell Mol Biol,2000,23 (5):646-651.
    26. Bamhart B, Ford GS, Bhushan A, et al. A polymorphic CD40 ligand(CD154)molecule mediates CD40-dependent signaling but interferes with the ability of soluble CD40 to functionally block CD154:CD40 interactions[J].Immunology,2000,99(1):54 -61.
    27. Hermann A, Rauch BH, Braun M, et al. Platelet CD40 ligand(CD40L)-subcelluar localization,regulation of expression,and inhibition by clopidogrel[J].Platelets,2001, 12(2) :74 -82.
    28.Pitchrord SC,Momi S,Giannini S,et al.Platelet P-selectin is required for pulmonary eosinophil and lymphocyte recruitment in a murine model of allergic inflammation[J].Blood,2005,105(5):2074-2081.
    29.雷伟,黄建安,陈延斌,等联合吸人沙美特罗/丙酸氟替卡松对哮喘患者血小板膜蛋白分子表达的影响[J].临床荟萃,2005,20(17):974-976.
    30.Kowal K, Pampuch A, Kowal-Bielecka O, et al.Platelet activation in allergic asthma patients during a llergen challenge with Dermatophagoides pteronyssinus[J]. Clin Exp Allergy 2006,36(4):426-32.
    31.Chen G.Grotendorst G,Eicholtz,et al.GM-CSF increases airway smooth muscle cell connective tissue expression by inducing TGF-β receptors[J].AmJ,Physiol Lung Cell Mol Physiol,2002,284(3):548-556.
    32. Bartram U,Speer CP.The role of transforming growth factor βin lung development and disease[J].Chest,2004,125(2):754-765.
    33.Nakao A.Is TGF-beta1 the key to suppression of human asthma? [J].Trends Immunol,2001,22(3):115-118.
    34.Mak JW,Rousell J.Haddad EB,et al.Transforming growth factor-β1 inhibits β2-adrenoceptor gene transcription[J].Naunyn Schmiedeberg’s Arch Pharmacol,2002,362:520-525.
    35. Minshall EM,Leung DYM,Martin RJ,et al.Eosipophil-assiociated TGF-β1 mRNA expression and airwalls fibrosis in bronchal asthma[J].Am J Pespir Cell Mol Biol,1997,17(3):326-333.
    36. McMillan SJ,Xanthou G, Lloyd CM.manipulation of allergen-induced airway remodeling by treatment with anti-TGFbeta antibody:effect on the smad signaling pathway[J].J Immunol,2005,174:5774-80.

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