Complement activation by both classical and alternative pathways is critical for the effector phase of arthritis

被引:92
作者
Hietala, MA
Nandakumar, KS
Persson, L
Fahlén, S
Holmdahl, R
Pekna, M
机构
[1] Univ Gothenburg, Dept Med Biochem, SE-40530 Gothenburg, Sweden
[2] Lund Univ, Dept Med Inflammat Res, Lund, Sweden
关键词
complement; rheumatoid arthritis; rodent; transgenic; knockout;
D O I
10.1002/eji.200424895
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
To analyze the role of the classical and alternative pathways of complement activation in the effector phase of arthritis, we have induced arthritis in C3- and factor B (FB)-deficient (C3(-/-) and FB-/-) DBA/1J mice using well-defined monoclonal IgG2b and IgG2a antibodies to type II collagen. In control DBA/1J mice, severe swelling of the joints, destruction of cartilage and erosion of bone developed very rapidly with a 100% incidence and a peak on days 7-10. Although 75% of C3(-/-) mice developed arthritis, the clinical severity was very mild and the onset was delayed. Severity of arthritis in FB-/- mice ranked intermediate in comparison with C3(-/-) and control mice with an incidence of 100%. Immunohistochemical analysis of the inflamed joints demonstrated substantial reduction in macrophage and neutrophilic leukocyte infiltration in both C3(-/-) and FB-/- mice, thereby confirming the clinical findings. We conclude that both the classical and the alternative pathways of complement activation are involved in the effector phase of arthritis.
引用
收藏
页码:1208 / 1216
页数:9
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