Complement in disease: a defence system turning offensive.
Complement in disease: a defence system turning offensive.
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DOI：
10.1038/nrneph.2016.70
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发表时间：
2016-07
期刊：
影响因子：
--
通讯作者：
Lambris JD
中科院分区：
文献类型：
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作者：
Ricklin D;Reis ES;Lambris JD
虽然补体系统主要被认为是宿主防御系统，但也存在作为炎症介质的这种先天免疫途径的更通用但潜在更有害的一面。定义补体系统控制微生物威胁和消除细胞碎片的能力的活动-例如感知分子危险模式，产生即时效应物，并与其他防御途径广泛协调-可以快速将补体从防御系统转变为驱动免疫和炎症疾病的侵略者。随着年龄的增长，这些宿主攻击行为变得更加明显，并因各种遗传因素和自身免疫反应而加剧。补体也可能被不适当地激活，例如响应于生物材料或移植物。在过去的二十年里，大量的研究已经导致对补体激活的理解越来越精细，确定了生理和病理行为之间的临界点，并揭示了治疗干预的途径。这篇综述总结了我们目前对补体系统的关键激活、调节和效应机制的看法，突出了重要的串扰连接，并重点讨论了肾脏疾病和移植，讨论了补体在临床条件和有前途的治疗方法中的参与。
Although the complement system is primarily perceived as a host defence system, a more versatile, yet potentially more harmful side of this innate immune pathway as an inflammatory mediator also exists. The activities that define the ability of the complement system to control microbial threats and eliminate cellular debris — such as sensing molecular danger patterns, generating immediate effectors, and extensively coordinating with other defence pathways — can quickly turn complement from a defence system to an aggressor that drives immune and inflammatory diseases. These host-offensive actions become more pronounced with age and are exacerbated by a variety of genetic factors and autoimmune responses. Complement can also be activated inappropriately, for example in response to biomaterials or transplants. A wealth of research over the past two decades has led to an increasingly finely tuned understanding of complement activation, identified tipping points between physiological and pathological behaviour, and revealed avenues for therapeutic intervention. This Review summarizes our current view of the key activating, regulatory, and effector mechanisms of the complement system, highlighting important crosstalk connections, and, with an emphasis on kidney disease and transplantation, discusses the involvement of complement in clinical conditions and promising therapeutic approaches.