The role of complement in inflammatory diseases from behind the scenes into the spotlight
The role of complement in inflammatory diseases from behind the scenes into the spotlight
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DOI：
10.2353/ajpath.2007.070166
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发表时间：
2007-09-01
影响因子：
6
通讯作者：
Lambris, John D.
中科院分区：
文献类型：
--
作者：
Markiewski, Maciej M.;Lambris, John D.
自补体系统最初被发现以来，我们对其生物学的理解经历了巨大的转变。这个系统传统上主要被描述为体液免疫的“补充”，现在则被视为先天免疫的核心组成部分，它保护宿主免受病原体侵害，在炎症过程中协调各种事件，并连接先天免疫和适应性免疫反应。补体是在血液、体液以及细胞表面发现的一组蛋白质。可溶性补体成分形成蛋白水解级联反应，其激活会导致产生针对免疫反应中各种细胞的补体效应分子。膜结合受体和调节因子将补体效应分子的信号传递给靶细胞，并将补体激活限制在病原体以及受损或被激活的宿主细胞表面。补体蛋白质、免疫细胞和介质之间的多种相互联系为保护机体免受感染以及支持受损组织修复提供了一种极好的机制。然而，这种“防御机制”的紊乱会导致多种疾病的发病机制。补体在各种炎症性疾病中的作用是多方面的，例如，补体的激活可显著导致炎症介导的组织损伤，而遗传性或获得性补体缺陷则极有利于自身免疫的发展。
Our understanding of the biology of the complement system has undergone a drastic metamorphosis since its original discovery. This system, which was traditionally primarily described as a "complement" to humoral immunity, is now perceived as a central constituent of innate immunity, defending the host against pathogens, coordinating various events during inflammation, and bridging innate and adaptive immune responses. Complement is an assembly of proteins found in the blood and body fluids and on cell surfaces. Soluble complement components form the proteolytic cascade, whose activation leads to the generation of complement effectors that target various cells involved in the immune response. Membrane-bound receptors and regulators transmit signals from complement effectors to target cells and limit complement activation to the surfaces of pathogens and damaged or activated host cells. The multiple interconnections among complement proteins, immune cells, and mediators provide an excellent mechanism to protect the organism against infections and support the repair of damaged tissues. However, disturbances in this "defense machinery" contribute to the pathogenesis of various diseases. The role of complement in various inflammatory disorders is multifaceted, for example, the activation of complement can significantly contribute to inflammation-mediated tissue damage, whereas inherited or acquired complement deficiencies highly favor the development of antoimmunity.