New insights of an old defense system: structure, function, and clinical relevance of the complement system.
New insights of an old defense system: structure, function, and clinical relevance of the complement system.
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DOI：
10.2119/molmed.2010.00149
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发表时间：
2011-03
期刊：
影响因子：
--
通讯作者：
Huber-Lang M
中科院分区：
文献类型：
--
作者：
Ehrnthaller C;Ignatius A;Gebhard F;Huber-Lang M
一个世纪前，该系统是作为先天免疫的潜在防御级联。但是，通过感测和清除受伤的细胞的病原体和危险防御的有益功能，对完成系统及其临床序列有了更明显的见解。败血症，多器官功能障碍，缺血/再灌注，心血管疾病等过程构成了新发现的三种著名的激活途径。凝血的串联蛋白酶尤其能够产生C5a，这不仅在病原体和感染/受损的组织中起决定性作用，而且在不受控制的情况下也是如此。产生的，导致健康的宿主组织的破坏该综述提供了包括这种古老的防御系统的结构功能关系的方法，提供了补充介导的临床相关疾病的新见解以及补体调制策略和当前研究方面的发展。
The complement system was discovered a century ago as a potent defense cascade of innate immunity. After its first description, continuous experimental and clinical research was performed, and three canonical pathways of activation were established. Upon activation by traumatic or surgical tissue damage, complement reveals beneficial functions of pathogen and danger defense by sensing and clearing injured cells. However, the latest research efforts have provided a more distinct insight into the complement system and its clinical subsequences. Complement has been shown to play a significant role in the pathogenesis of various inflammatory processes such as sepsis, multiorgan dysfunction, ischemia/reperfusion, cardiovascular diseases and many others. The three well-known activation pathways of the complement system have been challenged by newer findings that demonstrate direct production of central complement effectors (for example, C5a) by serine proteases of the coagulation cascade. In particular, thrombin is capable of producing C5a, which not only plays a decisive role on pathogens and infected/damaged tissues, but also acts systemically. In the case of uncontrolled complement activation, “friendly fire” is generated, resulting in the destruction of healthy host tissue. Therefore, the traditional research that focuses on a mainly positive-acting cascade has now shifted to the negative effects and how tissue damage originated by the activation of the complement can be contained. In a translational approach including structure-function relations of this ancient defense system, this review provides new insights of complement-mediated clinical relevant diseases and the development of complement modulation strategies and current research aspects.
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