A protective role for the fifth complement component (C5) in allergic airway disease
A protective role for the fifth complement component (C5) in allergic airway disease
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DOI：
10.1164/rccm.200503-334oc
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发表时间：
2006-04-15
影响因子：
24.7
通讯作者：
Wetsel, RA
中科院分区：
文献类型：
--
作者：
Droulin, SM;Sinha, M;Wetsel, RA
理论基础：我们实验室的报告以及其他实验室的报告都证明了补体激活、C3a过敏毒素及其受体C3aR在促进支气管肺过敏小鼠模型的Th2效应功能方面的重要性。虽然补体第五组分(CS)的缺乏与小鼠的呼吸道高反应性增强有关，但C5对哮喘其他主要生物学特征的贡献尚未得到评估。目的：因此，通过建立C5充足和C5缺乏的小鼠支气管肺过敏小鼠模型，评估C5对实验性哮喘的肺部炎症和Th2效应功能的影响。方法和主要结果：与已报道的C3和C3aR缺陷小鼠相比，C5缺陷小鼠在抗原攻击后表现出明显高于野生型同源对照小鼠的气道高反应性。此外，与受到攻击的野生型小鼠相比，C5缺陷小鼠的气道嗜酸性粒细胞和肺白介素4产生细胞的水平分别增加了3.4倍和2.7倍。与IL-4产生细胞数量一致，C5基因缺陷小鼠肺泡灌洗液中Th2细胞因子IL-5和IL-13水平升高，血清总IgE和抗原特异性IgE水平升高。结论：C5通过抑制炎症反应和Th2效应功能在变态反应性肺疾病中发挥重要保护作用。C5的存在提供的保护可能是由C5a介导的，这表明C5a可能在缓和Th2驱动的疾病(如哮喘)的炎症方面发挥重要作用。
Rationale: Reports from our laboratory, as well as those from others, have documented the importance of complement activation, the C3a anaphylatoxin, and its receptor, C3aR, in promoting Th2 effector functions in a mouse model of bronchopulmonary allergy. Although deficiency in the fifth complement component (CS) has been linked to enhanced airway hyperresponsiveness in mice, the contribution of C5 to other major biological hallmarks of asthma has not been evaluated.Objective: Accordingly, congenic C5-sufficient and C5-deficient mice were subjected to a mouse model of bronchopulmonary allergy to assess the impact of C5 on pulmonary inflammation and Th2 effector functions in experimental asthma.Methods and Main Results: In contrast to observations reported for C3- and C3aR-deficient animals, C5-deficient mice exhibited significantly increased airway hyperresponsiveness relative to wild-type congenic control mice after antigen challenge. Moreover, challenged C5-deficient mice had a 3.4-fold and 2.7-fold increase in the levels of airway eosinophils and lung interleukin (IL)-4-producing cells, respectively, compared with challenged wild-type mice. Consistent with the numbers of IL-4-producing cells, C5-deficient mice also had increased bronchoalveolar lavage levels of the Th2 cytokines IL-5 and IL-13 and elevated serum levels of total and antigen-specific IgE.Conclusions: These data indicate that C5 plays an important protective role in allergic lung disease by suppressing inflammatory responses and Th2 effector functions observed in this experimental model. The protection provided by the presence of C5 is likely mediated by C5a, suggesting that C5a may play a significant role in tempering inflammation in Th2-driven diseases such as asthma.