Distinct mechanisms of platelet aggregation as a consequence of different shearing flow conditions
Distinct mechanisms of platelet aggregation as a consequence of different shearing flow conditions
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DOI：
10.1172/jci973
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发表时间：
1998-01-15
影响因子：
15.9
通讯作者：
Ruggeri, ZM
中科院分区：
文献类型：
--
作者：
Goto, S;Ikeda, Y;Ruggeri, ZM
血小板聚集有助于阻止伤口部位的出血，但可能导致动脉粥样硬化血管闭塞，从而减少流向重要器官的血流。根据目前的教条，整合素α（IIb）β（3）通过与纤维蛋白原或vWf的相互作用在将血小板彼此连接中起排他性作用。我们在此证明，根据剪切流条件，该过程可能需要vWf与糖蛋白Ib α结合，即使α（IIb）β（3）能够结合粘附配体。仅由高剪切应力诱导的血小板活化由糖蛋白Ib α与vWf的相互作用引发，但只有当后者能够同时结合α（IIb）β（3）时才导致聚集。相反，当纤维蛋白原是α（IIb）β（3）粘附配体时，在被外源性激动剂如ADP和肾上腺素活化后暴露于高剪切速率的血小板可以聚集，但只有当vWf与糖蛋白Ib α结合时才能发生。因此，后者的相互作用似乎提供了一个键，克服高剪切速率的影响，并启动血小板间的凝聚力所必需的生物力学性能。这些发现强调了两种粘附受体在不同流体动力学条件下介导血小板聚集的不同功能，并修改了目前对止血和血栓形成关键事件的解释。
Platelet aggregation contributes to arresting bleeding at wound sites, but may cause occlusion of atherosclerotic vessels, thus curtailing blood flow to vital organs. According to current dogma, the integrin alpha(IIb)beta(3) plays an exclusive role in linking platelets to one another through interactions with fibrinogen or vWf. We demonstrate here that, depending on shearing flow conditions, this process may require vWf binding to glycoprotein Ib alpha, even when alpha(IIb)beta(3) is competent to bind adhesive ligands. Platelet activation induced solely by high shear stress is initiated by glycoprotein Ib alpha interaction with vWf, but results in aggregation only if the latter can bind concurrently to alpha(IIb)beta(3) In contrast, platelets exposed to high shear rate after activation by exogenous agonists such as ADP and epinephrine can aggregate when fibrinogen is the alpha(IIb)beta(3) adhesive ligand, yet only if vWf binding to glycoprotein Ib alpha can also occur. Thus, the latter interaction appears to provide a bond with biomechanical properties necessary to overcome the effects of high shear rate and initiate interplatelet cohesion. These findings highlight the distinct function of two adhesive receptors mediating platelet aggregation under varying fluid dynamic conditions, and modify the current interpretation of a crucial event in hemostasis and thrombosis.