Inhibition of complement activation decreases airway inflammation and hyperresponsiveness.
Inhibition of complement activation decreases airway inflammation and hyperresponsiveness.
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抑制补体激活可减少气道炎症和高反应性。
DOI：
10.1164/rccm.200306-739oc
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Gelfand,ErwinW
中科院分区：
文献类型：
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作者：
Taube,Christian;Rha,Yeong-Ho;Takeda,Katsuyuki;Park,Jung-Won;Joetham,Anthony;Balhorn,Annette;Dakhama,Azzeddine;Giclas,PatriciaC;Holers,VMichael;Gelfand,ErwinW
在小鼠模型中的研究表明，补体过敏毒素（C3 a和C5 a）参与过敏性哮喘的发生。我们研究了致敏后但在变应原激发前抑制补体活化对过敏性气道炎症和气道高反应性发展的影响。为了防止补体激活，我们使用了与IgG 1铰链、CH 2和CH 3结构域（Crry-Ig）融合的重组可溶形式的小鼠膜补体抑制剂补体受体相关基因y（Crry），其对经典和替代补体途径具有衰变加速活性，并对因子I介导的C3 b和C4 b裂解具有辅因子活性。用卵清蛋白致敏（第1天和第14天）并激发（第24-26天）C57 BL/6小鼠。在过敏原致敏后，在过敏原激发前通过腹膜内注射或雾化给予Crry-Ig。Crry-Ig显著防止气道高反应性的发展，降低气道和肺嗜酸性粒细胞增多以及肺淋巴细胞的数量，降低支气管肺泡灌洗液中白细胞介素（IL）-4，IL-5和IL-13的水平，降低血清卵清蛋白特异性IgE和IgG 1。这些结果表明，预防补体激活可能在治疗过敏性气道炎症和哮喘的致敏个体的治疗作用。
Studies in murine models have suggested the involvement of the complement anaphylatoxins (C3a and C5a) in the development of allergic asthma. We investigated the effects of inhibiting complement activation after sensitization but before allergen challenge on the development of allergic airway inflammation and airway hyperresponsiveness. To prevent complement activation, we used a recombinant soluble form of the mouse membrane complement inhibitor complement receptor-related gene y (Crry) fused to the IgG1 hinge, CH2 and CH3 domains (Crry-Ig), which has decay-accelerating activity for both the classic and alternative pathways of complement as well as cofactor activity for factor I-mediated cleavage of C3b and C4b. C57BL/6 mice were sensitized (Days 1 and 14) and challenged (Days 24–26) with ovalbumin. Crry-Ig was administered after allergen sensitization either as an intraperitoneal injection or by nebulization before allergen challenge. Crry-Ig significantly prevented the development of airway hyperresponsiveness, decreased airway and lung eosinophilia as well as the numbers of lung lymphocytes, decreased levels of interleukin (IL)-4, IL-5, and IL-13 in bronchoalveolar lavage fluid and decreased serum ovalbumin-specific IgE and IgG1. These results suggest that prevention of complement activation may have a therapeutic role in the treatment of allergic airway inflammation and asthma in sensitized individuals.