[Complement activation and inflammation].
[Complement activation and inflammation].
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发表时间：
2006-07
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通讯作者：
M. Abe
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作者：
M. Abe
补体系统不仅在防御系统中发挥重要作用，如果过度激活或控制不当，也会导致炎症的放大。通过三种途径之一的补体激活受到各种补体激活调节剂（RCA）的严格控制，这些调节剂在各种细胞上组成性表达，以限制过度激活。补体激活可产生多肽，即所谓的过敏毒素和大分子质量的膜攻击复合物（MAC）。由补体激活产生的过敏毒素（C3a， C4a和C5a）被认为是先天免疫和获得性免疫的桥梁。考虑到C5a比C3a更有效，但C3的血清浓度是C5的10倍，C3a的整体效果可能与C5a相当。由于这两种过敏毒素都被认为是通过视紫红质型受体发挥作用，它们的受体拮抗剂是发现抗炎和免疫调节药物的目标。补体活化可能与各种难治性疾病的病理生理有关，包括ARDS、哮喘、脓毒性综合征、SLE、类风湿关节炎、缺血再灌注损伤、牛皮癣等。补体系统的药理学操作可能包括多种策略，包括(1)不同水平的补体活化抑制剂，(2)过敏毒素、C3a和C5a的受体拮抗剂，以及(3)包括单克隆抗体在内的C5a抑制剂。与上述手法有关的候选药剂已经生产出来，其中一些正在对某些疾病患者进行临床试验。
The complement system not only plays an important role in the defense system, but also contributes to the amplification of inflammation if activated in excess or inappropriately controlled. Complement activation through one of three pathways is tightly controlled by various regulators of complement activation (RCA) which are constitutively expressed on various cells in order to restrict excessive activation. Complement activation may generate polypeptides, so-called anaphylatoxins, and membrane attack complex (MAC) with large molecular mass. Anaphylatoxins (C3a, C4a, and C5a) produced by activation of the complement is considered to bridge innate and acquired immunity. Considering that C5a is more potent than C3a, but the serum concentration of C3 is 10 times higher than that of C5, the overall effects of C3a may be comparative with those of C5a. Since both anaphylatoxins are considered to exert their actions through rhodopsin-typed receptors, their receptor antagonists are targets for the discovery of anti-inflammatory and immune-modulating drugs. Complement activation may be related to the pathophysiology of various refractory disorders including ARDS, asthma, septic syndrome, SLE, rheumatoid arthritis, ischemia-reperfusion injury, and psoriasis etc. Pharmacological manipulation of the complement system may consist of various strategies including (1) inhibitors of complement activation at various levels, (2) receptor antagonists of anaphylatoxins, C3a and C5a, and (3) inhibitors of C5a including monoclonal antibody. Candidate agents concerning the above-mentioned manipulations have being produced and some are now in progress toward clinical trials in patients with certain diseases.