Identification of complement factor 5 as a susceptibility locus for experimental allergic asthma
Identification of complement factor 5 as a susceptibility locus for experimental allergic asthma
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DOI：
10.1038/79759
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发表时间：
2000-09-01
影响因子：
30.5
通讯作者：
Wills-Karp, M
中科院分区：
文献类型：
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作者：
Karp, CL;Grupe, A;Wills-Karp, M
过敏性哮喘的患病率和严重程度持续上升，迫切需要寻找环境触发因素和遗传底物。使用肺基因表达的微阵列分析和基于单核苷酸多态性的基因分型，结合数量性状位点分析，我们确定了编码补体因子5（CS）的基因作为过敏原诱导的哮喘小鼠模型气道高反应性的易感位点。CS编码序列的缺失导致C5缺陷和易感性。白细胞介素12（IL-12）能够预防或逆转实验性过敏性哮喘。阻断C5 a受体使人单核细胞不能产生IL-12，模拟C5缺陷小鼠巨噬细胞产生IL-12的钝化，并提供了C5调节哮喘易感性的机制。补体在调节哮喘易感性中的作用突出了免疫调节事件在疾病发病机制中先天免疫和适应性免疫界面的重要性。
The prevalence and severity of allergic asthma continue to rise, lending urgency to the search for environmental triggers and genetic substrates. Using microarray analysis of pulmonary gene expression and single nucleotide polymorphism-based genotyping, combined with quantitative trait locus analysis, we identified the gene encoding complement factor 5 (CS) as a susceptibility locus for allergen-induced airway hyperresponsiveness in a murine model of asthma. A deletion in the coding sequence of CS leads to C5-deficiency and susceptibility. Interleukin 12 (IL-12) is able to prevent or reverse experimental allergic asthma. Blockade of the C5a receptor rendered human monocytes unable to produce IL-12, mimicking blunted IL-12 production by macrophages from C5-deficient mice and providing a mechanism for the regulation of susceptibility to asthma by C5. The role of complement in modulating susceptibility to asthma highlights the importance of immunoregulatory events at the interface of innate and adaptive immunity in disease pathogenesis.