Complement activation pathways in murine immune complex-induced arthritis and in C3a and C5a generation in vitro
Complement activation pathways in murine immune complex-induced arthritis and in C3a and C5a generation in vitro
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DOI：
10.1111/j.1365-2249.2009.04035.x
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发表时间：
2010-01-01
影响因子：
4.6
通讯作者：
Arend, W. P.
中科院分区：
文献类型：
--
作者：
Banda, N. K.;Levitt, B.;Arend, W. P.
在小鼠胶原抗体诱导的关节炎（CAIA）模型中，补体旁路途径（AP）可单独介导免疫复合物诱导的关节炎。是否经典途径（CP）或凝集素途径（LP）单独可以介导CAIA是未知的。使用不同补体成分遗传缺陷的小鼠，我们在此报道的结果证实单独的CP和LP各自不能介导CAIA。CP引起的C3和/或C5活化水平较低或不存在可能是AP在CAIA和许多鼠疾病模型中的重要性的可能解释。此外，其他研究者报道小鼠血清中不存在CP C5转化酶活性。为了解决这些问题，我们采用了体外系统的粘附免疫球蛋白（IG）G诱导的补体激活使用板包被鼠抗胶原单克隆抗体（mAb）。这些实验在灭活CP（Ca++缺乏）或AP（抑制因子B的mAb）的条件下使用补体缺陷型小鼠血清和野生型小鼠或正常人血清。在小鼠和人血清中均观察到单独使用AP或CP可稳健生成C3 a和C5 a，尽管血清种属之间存在一些小差异。我们的结论是，无论是CP或LP单独是能够介导的CAIA在体内和小鼠血清表现出高水平的IgG诱导的C5 a生成在体外通过CP或AP。
P>The alternative pathway (AP) of complement alone is capable of mediating immune complex-induced arthritis in the collagen antibody-induced arthritis (CAIA) model in mice. Whether the classical pathway (CP) or lectin pathway (LP) alone can mediate CAIA is not known. Using mice genetically deficient in different complement components, our results reported herein establish that the CP and LP alone are each incapable of mediating CAIA. A lower level or absence of C3 and/or C5 activation by the CP may be possible explanations for the importance of the AP in CAIA and in many murine models of disease. In addition, other investigators have reported that CP C5 convertase activity is absent in mouse sera. To address these questions, we employed an in vitro system of adherent immunoglobulin (Ig)G-induced complement activation using plates coated with murine anti-collagen monoclonal antibody (mAb). These experiments used complement-deficient mouse sera and wild-type mouse or normal human sera under conditions inactivating either the CP (Ca++ deficiency) or the AP (mAb inhibitory to factor B). Robust generation of both C3a and C5a by either the AP or CP alone were observed with both mouse and human sera, although there were some small differences between the species of sera. We conclude that neither the CP nor LP alone is capable of mediating CAIA in vivo and that mouse sera exhibits a high level of IgG-induced C5a generation in vitro through either the CP or AP.