The alternative pathway of complement in disease: opportunities for therapeutic targeting
The alternative pathway of complement in disease: opportunities for therapeutic targeting
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DOI：
10.1016/j.molimm.2004.03.012
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发表时间：
2004-06-01
影响因子：
3.6
通讯作者：
Thurman, JM
中科院分区：
文献类型：
--
作者：
Holers, VM;Thurman, JM
补体的旁路途径作为治疗靶点越来越受到关注，因为最近在几种动物模型中的发现支持其在组织损伤和疾病发病机制中的重要作用。尽管旁路途径激活对体外血清补体激活的贡献相对较小，但其在血管外部位产生活化的促炎片段中的作用是显著的。几种潜在的机制可能是这种夸大的影响，包括替代途径成分的局部合成，疾病诱导的调节蛋白的改变，以及含有替代途径成分的炎性细胞流入损伤部位。本文综述了几种动物模型，其中替代途径是中央参与疾病的发病机制，并建议替代途径抑制剂作为人类疾病的治疗的潜在作用。预计第20届国际补体研讨会上将提交几项临床相关研究，以确定与该途径有关的其他感兴趣的领域。(C)2004爱思唯尔有限公司保留所有权利。
The alternative pathway of complement is receiving increasing attention as a therapeutic target because of recent findings in several animal models that support its essential role in tissue injury and disease pathogenesis. Although the contribution of alternative pathway activation to serum complement activation in vitro is relatively modest, its role in generating activated pro-inflammatory fragments at extra-vascular sites is substantial. Several potential mechanisms might underlie this exaggerated effect, including local synthesis of alternative pathway components, disease-induced alterations of regulatory proteins, and influx of inflammatory cells that contain alternative pathway components into sites of injury. This review examines several animal models in which the alternative pathway is centrally involved in disease pathogenesis and which suggest a potential role for alternative pathway inhibitors as therapies for human disease. It is also expected that several clinically relevant studies will be presented at the XXth International Complement Workshop that will identify additional areas of interest with regard to this pathway. (C) 2004 Elsevier Ltd. All rights reserved.