Department of Traumatology, Hand, Plastic, and Reconstructive Surgery, Center of Surgery, Center of Musculoskeletal Research, University of Ulm, Ulm, Germany.
Mol Med. 2011 Mar-Apr;17(3-4):317-29. doi: 10.2119/molmed.2010.00149. Epub 2010 Oct 29.
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.
补体系统在一个世纪前被发现，是先天免疫的强大防御级联反应。在首次描述之后，进行了持续的实验和临床研究，并建立了三个经典的激活途径。在创伤或手术组织损伤激活后，补体通过感知和清除受损细胞，揭示了病原体和危险防御的有益功能。然而，最新的研究努力为补体系统及其临床后果提供了更清晰的认识。补体已被证明在各种炎症过程的发病机制中发挥重要作用，如败血症、多器官功能障碍、缺血/再灌注、心血管疾病等。补体系统的三个著名激活途径受到了新发现的挑战，这些新发现表明凝血级联中的丝氨酸蛋白酶可以直接产生中央补体效应物（例如 C5a）。特别是，凝血酶能够产生 C5a，它不仅对病原体和感染/受损组织起决定性作用，而且还在全身起作用。在补体失控激活的情况下，会产生“友军火力”，导致健康宿主组织的破坏。因此，传统上专注于主要积极作用级联的研究现在已经转向关注补体激活引起的组织损伤的负面影响以及如何加以控制。在包括该古老防御系统的结构-功能关系的转化方法中，本综述提供了补体介导的临床相关疾病的新见解，以及补体调节策略的发展和当前的研究方面。
