Hietala Max Albert, Nandakumar Kutty S, Persson Linda, Fahlén Susann, Holmdahl Rikard, Pekna Marcela
Department of Medical Biochemistry, Göteborg University, Göteborg, Sweden.
Eur J Immunol. 2004 Apr;34(4):1208-16. doi: 10.1002/eji.200424895.
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.
为分析补体激活的经典途径和替代途径在关节炎效应阶段中的作用，我们使用针对II型胶原的明确单克隆IgG2b和IgG2a抗体，在C3缺陷和B因子（FB）缺陷（C3(-/-)和FB(-/-)）的DBA/1J小鼠中诱导了关节炎。在对照DBA/1J小鼠中，关节严重肿胀、软骨破坏和骨质侵蚀发展非常迅速，发病率为100%，在第7 - 10天达到峰值。虽然75%的C3(-/-)小鼠发生了关节炎，但临床严重程度非常轻微且发病延迟。与C3(-/-)小鼠和对照小鼠相比，FB(-/-)小鼠的关节炎严重程度居中，发病率为100%。对发炎关节的免疫组织化学分析表明，C3(-/-)和FB(-/-)小鼠中的巨噬细胞和嗜中性白细胞浸润均显著减少，从而证实了临床发现。我们得出结论，补体激活的经典途径和替代途径均参与了关节炎的效应阶段。
