A revised model of platelet aggregation
A revised model of platelet aggregation
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DOI：
10.1172/jci7569
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发表时间：
2000-03-01
影响因子：
15.9
通讯作者：
Jackson, SP
中科院分区：
文献类型：
--
作者：
Kulkarni, S;Dopheide, SM;Jackson, SP
在这项研究中，我们已经研究了血小板聚集的机制，在生理流动条件下，使用体外流动为基础的血小板聚集试验和在体内大鼠血栓形成模型。我们的研究证明了血小板聚集过程的意想不到的复杂性，其中流动血液中的血小板在动脉和静脉剪切速率下连续地束缚、移位和/或从生长的血小板血栓的管腔表面分离。对血管性血友病因子（vWf）或整合素α（IIb）β（3）先天性缺陷的血小板的研究表明，血小板vWfin介导血小板束缚和易位，而整合素α（IIb）β（3）介导细胞阻滞的关键作用。流动状态下的血小板聚集似乎是一个多步骤过程，涉及：（a）固定血小板表面的vWf暴露;（B）自由流动血小板表面的GPI B α与固定血小板表面的vWf结合介导的血小板聚集的可逆阶段;（c）依赖于整合素α（II B）β的聚集的不可逆阶段（3）。对体内血小板血栓形成的研究表明，这种多步粘附机制对于血小板在小动脉中的聚集是必不可少的，并且似乎还促进血小板在小静脉中的聚集体形成。总之，我们的研究证明了血小板vWfin在流动下启动血小板聚集过程的重要作用，并挑战了目前公认的观点，即vWf-GPIb α相互作用仅涉及在升高的剪切速率下启动血小板聚集。
In this study we have examined the mechanism of platelet aggregation under physiological flow conditions using an in vitro flow-based platelet aggregation assay and an in vivo rat thrombosis model. Our studies demonstrate an unexpected complexity to the platelet aggregation process in which platelets in flowing blood continuously tether, translocate, and/or detach from the luminal surface of a growing platelet thrombus at both arterial and venous shear rates. Studies of platelets congenitally deficient in von Willebrand factor (vWf) or integrin alpha(IIb)beta(3) demonstrated a key role for platelet vWfin mediating platelet tethering and translocation, whereas integrin alpha(IIb)beta(3) mediated cell arrest. Platelet aggregation under flow appears to be a multistep process involving: (a) exposure of vWfon the surface of immobilized platelets; (b) a reversible phase of platelet aggregation mediated by the binding of GPIb alpha on the surface of free-flowing platelets to vWf on the surface of immobilized platelets; and (c) an irreversible phase of aggregation dependent on integrin alpha(IIb)beta(3). studies of platelet thrombus formation in vivo demonstrate that this multistep adhesion mechanism is indispensable for platelet aggregation in arterioles and also appears to promote platelet aggregate formation in venules. Together, our studies demonstrate an important role for platelet vWfin initiating the platelet aggregation process under flow and challenge the currently accepted view that the vWf-GPIb alpha interaction is exclusively involved in initiating platelet aggregation at elevated shear rates.