Abstract:
The complement system plays a dual role in the body, either as a first-line defense barrier when balanced between activation and inhibition or as a potential driver of complement-associated injury or diseases when unbalanced or over-activated. C4b-binding protein (C4BP) was the first circulating complement regulatory protein identified and it functions as an important complement inhibitor. C4BP can suppress the over-activation of complement components and prevent the complement system from attacking the host cells through the binding of complement cleavage products C4b and C3b, working in concert as a cofactor for factor I in the degradation of C4b and C3b, and consequently preventing or reducing the assembly of C3 convertase and C5 convertase, respectively. C4BP, particularly C4BP α-chain (C4BPα), exerts its unique inhibitory effects on complement activation and opsonization, systemic inflammation, and platelet activation and aggregation. It has long been acknowledged that crosstalk or interplay exists between the complement system and platelets. Our unpublished preliminary data suggest that circulating C4BPα exerts its antiplatelet effects through inhibition of both complement activity levels and complement-induced platelet reactivity. Plasma C4BPα levels appear to be significantly higher in patients sensitive to, rather than resistant to, clopidogrel, and we suggest that a plasma C4BPα measurement could be used to predict clopidogrel resistance in the clinical settings.
摘要:
补体系统在身体中起着双重作用,在激活和抑制之间达到平衡时作为一线防御屏障,或者在不平衡或过度激活时作为补体相关损伤或疾病的潜在驱动因素。C4b结合蛋白(C4BP)是第一个被鉴定的循环补体调节蛋白,它是一种重要的补体抑制剂。C4BP可以抑制补体成分的过度活化,防止补体系统通过补体裂解产物C4b和C3b的结合攻击宿主细胞,在C4b和C3b的降解中作为因子I的辅因子协同工作,从而阻止或减少C3转化酶和C5转化酶的组装,分别。C4BP,特别是C4BPα链(C4BPα),对补体激活和调理作用发挥其独特的抑制作用,全身性炎症,和血小板活化和聚集。长期以来,人们已经认识到在补体系统和血小板之间存在串扰或相互作用。我们未发表的初步数据表明,循环C4BPα通过抑制补体活性水平和补体诱导的血小板反应性来发挥其抗血小板作用。血浆C4BPα水平似乎明显高于敏感患者,而不是抵抗,氯吡格雷,我们建议血浆C4BPα测量可用于预测临床环境中的氯吡格雷抵抗。