Decay accelerating factor (CD55).
Decay accelerating factor (CD55).
复制标题
DOI：
10.1007/978-3-642-77014-2_2
复制
发表时间：
1992
影响因子：
--
通讯作者：
A. Nicholson‐Weller
中科院分区：
文献类型：
--
作者：
A. Nicholson‐Weller
补体是由12种激活蛋白和至少11种抑制剂组成的介体系统。活化蛋白依次相互作用以产生具有特异性和有效生物活性的切割片段和缩合产物。活化的补体蛋白可作为过敏毒素、粘附因子、趋化因子、调理素和可裂解的跨膜孔发挥作用（综述见FRIES和FRANK 1987）。受调节的补体激活对于宿主的存活是必不可少的，而不受调节的补体激活有助于炎症并且对宿主有害。补体受其活化的特异性、其活化产物的不稳定性以及在宿主细胞的液相和膜内发现的有效抑制剂的调节。本文综述了补体的一个重要膜调节因子--衰变加速因子（decay accelerating factor，OAF）的结构、功能和表达，概括地说，补体的激活要么是通过特异性抗体与抗原结合激活C1，启动经典途径，要么是通过外源表面组装C3 bBb酶，在旁路途径中裂解C3。在经典途径的活化过程中，C1裂解C4，主要裂解片段C4 b结合到C1附近的靶细胞膜上。然后C2与C4 b结合，并被C1切割形成双分子酶C4 b2 a，即所谓的C3转化酶，其切割并活化C3和C5。C2 a带有催化位点，并且该位点仅在C2 a片段与C4 b结合时才有活性。对于旁路途径，在液相中自发形成的C3 B b停靠在允许随后结合因子B的表面上。后者然后被因子0激活，因子0是一种循环活性丝氨酸酯酶。所得的C3 bBb转化酶可以切割并活化C3和C5。与经典转化酶的C2 a类似，Bb片段具有催化位点，并且该催化位点仅在Bb片段与C3 b结合时才具有活性。C3激活是一个关键步骤，因为它是替代途径和经典途径会聚的地方：经典途径对C3的裂解使得有可能招募替代途径，即所谓的扩增环。此外，大多数补体介质在C3裂解步骤或之后产生。调节C3活化的重要性反映在以下事实中：存在至少三种流体相抑制剂和三种膜调节剂，包括OAF，其在该步骤起作用。
Complement is a mediator system comprised of 12 activation proteins and at least 11 inhibitors. The activation proteins interact sequentially to generate cleavage fragments and condensation products with specific and potent biologic activity. Activated complement proteins can function as anaphylatoxins, adherence factors, chemotaxins, opsonins, and a transmembrane pore, which can be lytic (reviewed in FRIES and FRANK 1987). Regulated complement activation is essential for the survival of the host, while unregulated complement activation contributes to inflammation and is detrimental to the host. Complement is regulated by the specificity of its activation, by the lability of its activation products, and by the potent inhibitors found in the fluid phase and within the membranes of host cells. The structure, function, and expression of one important membrane regulator of complement, namely, the decay accelerating factor (OAF), will be reviewed here.In general terms, complement is activated either by specific antibody combining with its antigen and activating C1, initiating the classical pathway, or by foreign surfaces that permit the assembly of the C3bBb enzyme, which cleaves C3 in the alternative pathway. During activation of the classical pathway, C1 cleaves C4 and the major cleavage fragment C4b binds to the target cell membrane in the vicinity of C1. C2 then binds to C4b and is cleaved by C1 to form the bimolecular enzyme C4b2a, the so-called C3 convertase, which cleaves and activates C3 and C5. C2a bears the catalytic site, and this site is active only while the C2a fragment is bound to C4b. For the alternative pathway, C3b that is spontaneously formed in the fluid phase docks on a surface which allows the subsequent binding of factor B. The latter is then activated by factor 0, a circulating active serine esterase. The resultant C3bBb convertase can cleave and activate C3 and C5. Analogous to C2a of the classical convertase, it is the Bb fragment which bears the catalytic site, and that catalytic site is only active as long as the Bb fragment is bound to C3b. C3 activation is a critical step because it is where the alternative and classical pathways converge: cleavage of C3 by the classical pathway makes it potentially possible to recruit the alternative pathway, the so-called amplification loop. In addition, most of the mediators of complement are generated at the C3 cleavage step or later. The importance of regulating C3 activation is reflected in the fact that there are at least three fluid phase inhibitors and three membrane regulators, including OAF, which act at this step.