Stringent regulation of complement lectin pathway C3/C5 convertase by C4b-binding protein (C4BP).
Stringent regulation of complement lectin pathway C3/C5 convertase by C4b-binding protein (C4BP).
复制标题
C4b 结合蛋白 (C4BP) 对补体凝集素途径 C3/C5 转化酶的严格调节。
DOI：
10.1016/j.molimm.2009.07.006
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发表时间：
2009
影响因子：
3.6
通讯作者：
Salvi,VeenaP
中科院分区：
文献类型：
--
作者：
Rawal,Nenoo;Rajagopalan,Rema;Salvi,VeenaP
补体凝集素途径是先天免疫系统的重要组成部分，适合于快速识别感染，因为通过该途径沉积的每个C4 b能够形成C3/C5转化酶。在本研究中，C4 b结合蛋白（C4 BP）的作用，在调节凝集素途径C3/C5转化酶组装酵母聚糖和绵羊红细胞与甘露聚糖（EMan）。虽然抑制两个表面上表面结合的C3转化酶的50%（IC 50）形成的C4 BP浓度与可溶性C3转化酶（1.05 nM）相似，但需要103倍和41倍以上的浓度来抑制C5转化酶在酵母聚糖（2.81 nM）和EMan（42.66 nM）上的组装。没有观察到C4 BP和表面结合的C4 b单独或与C3 b复合之间的结合相互作用的差异。增加酵母聚糖上的C4 b密度（14，000 - 431，000 C4 b/Zym）使每个C4 BP结合的C4 b数量从2.87增加到8.23，表明在高C4 b密度下，C4 BP的所有七条α链都参与C4 b结合。相反，当EMan上的C4 b密度增加时，每个C4 BP结合的C4 b数量保持恒定（3.79±0.60）。数据还显示，C4 BP比经典途径C3/C5转化酶更严格地调节凝集素途径C3/C5转化酶的组装和衰变，因为对经由凝集素途径沉积的C4 b的亲和力比经典途径大107至13倍。因此，C4 BP有效地调节凝集素途径在产生C3/C5转化酶和因此产生促炎产物方面比经典途径大四倍的潜力，所述促炎产物是对抗感染所需的，但偶尔会引起病理性炎症反应。
The complement lectin pathway, an essential component of the innate immune system, is geared for rapid recognition of infections as each C4b deposited via this pathway is capable of forming a C3/C5 convertase. In the present study, role of C4b-binding protein (C4BP) in regulating the lectin pathway C3/C5 convertase assembled on zymosan and sheep erythrocytes coated with mannan (EMan) was examined. While the C4BP concentration for inhibiting 50% (IC50) formation of surface-bound C3 convertase on the two surfaces was similar to that obtained for the soluble C3 convertase (1.05nM), ∼3- and 41-fold more was required to inhibit assembly of the C5 convertase on zymosan (2.81nM) and EMan(42.66nM). No difference in binding interactions between C4BP and surface-bound C4b alone or in complex with C3b was observed. Increasing the C4b density on zymosan (14,000–431,000 C4b/Zym) increased the number of C4b bound per C4BP from 2.87 to 8.23 indicating that at high C4b density all seven α-chains of C4BP are engaged in C4b-binding. In contrast, the number of C4b bound per C4BP remained constant (3.79±0.60) when the C4b density on EManwas increased. The data also show that C4BP regulates assembly and decay of the lectin pathway C3/C5 convertase more stringently than the classical pathway C3/C5 convertase because of a ∼7- to 13-fold greater affinity for C4b deposited via the lectin pathway than the classical pathway. C4BP thus regulates efficiently the four times greater potential of the lectin pathway than the classical pathway in generating the C3/C5 convertase and hence production of pro-inflammatory products, which are required to fight infections but occasionally cause pathological inflammatory reactions.