Song Wen-Chao
Center for Experimental Therapeutics, Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pa., USA.
Curr Dir Autoimmun. 2004;7:181-99. doi: 10.1159/000075693.
The complement system plays a complex role in the pathogenesis of autoimmune diseases. It inhibits autoimmunity development by helping to maintain self-tolerance and/or by facilitating the disposal of immune complexes and apoptotic cell antigens. On the other hand, complement activation is thought to contribute significantly to end organ damage in antibody-mediated autoimmune and inflammatory conditions, although the relevant importance of complement and Fe receptor pathways in these processes has recently been debated. To avoid autologous complement-mediated tissue injury, host cells normally express a number of soluble and membrane-bound complement regulatory proteins. Recent studies with gene knockout mice have suggested that membrane-bound complement regulatory proteins may critically determine the sensitivity of host tissues to complement injury in autoimmune and inflammatory disorders. Evidence is also accumulating to support the hypothesis that membrane complement regulatory proteins may not only inhibit complement-mediated injury during the effector phase of autoimmunity but also influence the adaptive immune response through complement-dependent or -independent mechanisms. The latter mechanism is likely related to their potential as cell surface signaling molecules.
补体系统在自身免疫性疾病的发病机制中发挥着复杂的作用。它通过帮助维持自身耐受性和/或促进免疫复合物及凋亡细胞抗原的清除来抑制自身免疫的发展。另一方面，尽管补体和Fc受体途径在这些过程中的相关重要性最近存在争议，但补体激活被认为在抗体介导的自身免疫和炎症性疾病中对终末器官损伤有显著贡献。为避免自体补体介导的组织损伤，宿主细胞通常表达多种可溶性和膜结合的补体调节蛋白。最近对基因敲除小鼠的研究表明，膜结合补体调节蛋白可能在自身免疫和炎症性疾病中决定性地决定宿主组织对补体损伤的敏感性。越来越多的证据支持这样的假说，即膜补体调节蛋白不仅可以在自身免疫的效应阶段抑制补体介导的损伤，还可以通过补体依赖或非依赖机制影响适应性免疫反应。后一种机制可能与其作为细胞表面信号分子的潜力有关。
