Thrombin-induced conversion of fibrinogen to fibrin results in rapid platelet trapping which is not dependent on platelet activation or GPIb
Thrombin-induced conversion of fibrinogen to fibrin results in rapid platelet trapping which is not dependent on platelet activation or GPIb
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DOI：
10.1038/sj.bjp.0705095
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发表时间：
2003-02-01
影响因子：
7.3
通讯作者：
Watson, SP
中科院分区：
文献类型：
--
作者：
Jarvis, GE;Atkinson, BT;Watson, SP
1凝血酶对人血小板的激活是通过两个G蛋白偶联的蛋白酶激活受体PAR-1和PAR-4的蛋白水解性裂解而介导的。然而，凝血酶也能与血小板表面糖蛋白GPIB特异性结合。凝血酶可通过GPIB介导的一种新途径诱导血小板聚集，该途径不依赖于PAR激活和纤维蛋白原与α(IIb)β(3)整合素的结合，但依赖于纤维蛋白的聚合和细胞内信号的产生。最初的初始反应很小，但一致，与血小板颗粒的释放有关。延迟的二次反应更明显，并被纤维蛋白聚合阻滞肽GPR3所消除。3莫卡哈金部分切割GPIB的胞外部分，部分抑制凝血酶诱导的α(IIb)β(3)依赖的聚集和释放，但对次级纤维蛋白依赖的反应没有影响。4血小板的固定取消了α(IIb)β(3)依赖的腺嘌呤核苷酸的聚集和释放，而纤维蛋白依赖的反应仍然存在，表明血小板激活和细胞内信号传递不是这种次级‘聚集’所必需的。在纤维蛋白原和洛曲菲班存在下观察到的二次纤维蛋白依赖的‘聚集’反应是一种主要依赖于凝血酶将可溶性纤维蛋白原转化为聚合纤维蛋白的血小板捕获现象。
1 Activation of human platelets by thrombin is mediated by the proteolytic cleavage of two G-protein coupled protease-activated receptors, PAR-1 and PAR-4. However, thrombin also binds specifically to the platelet surface glycoprotein GPIb. It has been claimed that thrombin can induce aggregation of platelets via a novel GPIb-mediated pathway, which is independent of PAR activation and fibrinogen binding to alpha(IIb)beta(3) integrin, but dependent upon polymerizing fibrin and the generation of intracellular signals.2 In the presence of both fibrinogen and the alpha(IIb)beta(3) receptor antagonist lotrafiban, thrombin induced a biphasic platelet aggregation response. The initial primary response was small but consistent and associated with the release of platelet granules. The delayed secondary response was more substantial and was abolished by the fibrin polymerization blocking peptide GPRP.3 Cleavage of the extracellular portion of GPIb by mocarhagin partially inhibited thrombin-induced alpha(IIb)beta(3)-dependent aggregation and release, but had no effect on the secondary fibrin-dependent response.4 Fixing of the platelets abolished alpha(IIb)beta(3)-dependent aggregation and release of adenine nucleotides, whereas the fibrin-dependent response remained, indicating that platelet activation and intracellular signalling are not necessary for this secondary 'aggregation'.5 In conclusion, the secondary fibrin-dependent 'aggregation' response observed in the presence of fibrinogen and lotrafiban is a platelet trapping phenomenon dependent primarily on the conversion of soluble fibrinogen to polymerizing fibrin by thrombin.