Complement deficiency ameliorates collagen-induced arthritis in mice
Complement deficiency ameliorates collagen-induced arthritis in mice
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DOI：
10.4049/jimmunol.169.1.454
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发表时间：
2002-07-01
影响因子：
4.4
通讯作者：
Pekna, M
中科院分区：
文献类型：
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作者：
Hietala, MA;Jonsson, IM;Pekna, M
胶原诱导性关节炎(CIA)是以滑膜炎和进行性软骨、骨质破坏为特征的类风湿性关节炎的实验动物模型。CIA是通过注射异种或同种的胶原蛋白11型在易感的小鼠品系中诱导的。建立补体C3(C3(-/-))和B因子(FB-/-)缺乏的DBA/1J小鼠，探讨补体系统在CIA中的作用。用在CFA中乳化的牛11型胶原免疫对照组小鼠，出现了严重的关节炎和高的CII特异性抗体效价。相反，C3(-/-)和FB-/-对CIA具有高度的抵抗力，表现出较低的CII特异性免疫球蛋白抗体应答。在初始免疫后3wk，反复接触11型牛胶原蛋白可导致所有小鼠的抗体应答增加，并在补体缺乏的小鼠中引发关节炎。尽管C3(-/-)小鼠的关节炎评分很低，但FB-/-小鼠的关节炎在C3(-/-)小鼠和对照组小鼠中处于中等水平。我们得出结论，补体通过经典途径和替代途径激活在CIA中起着有害的作用。
Collagen-induced arthritis (CIA) is an experimental animal model of human rheumatoid arthritis being characterized by synovitis and progressive destruction of cartilage and bone. CIA is induced by injection of heterologous or homologous collagen type 11 in a susceptible murine strain. DBA/1J mice deficient of complement factors C3 (C3(-/-)) and factor B (FB-/-) were generated to elucidate the role of the complement system in CIA. When immunized with bovine collagen type 11 emulsified in CFA, control mice developed severe arthritis and high CII-specific IgG Ab titers. In contrast, the C3(-/-) and FB-/- were highly resistant to CIA and displayed decreased CII-specific IgG Ab response. A repeated bovine collagen type 11 exposure 3 wk after the initial immunization led to an increase in the Ab response in all mice and triggered arthritis also in the complement-deficient mice. Although the arthritic score of the C3(-/-) mice was low, the arthritis in FB-/- mice ranked intermediate with regard to C3(-/-) and control mice. We conclude that complement activation by both the classical and the alternative pathway plays a deleterious role in CIA.