GPVI and α2β1 play independent critical roles during platelet adhesion and aggregate formation to collagen under flow
GPVI and α2β1 play independent critical roles during platelet adhesion and aggregate formation to collagen under flow
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DOI：
10.1182/blood-2004-11-4434
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发表时间：
2005-08-15
期刊：
影响因子：
20.3
通讯作者：
Kahn, ML
中科院分区：
文献类型：
--
作者：
Sarratt, KL;Chen, H;Kahn, ML
在过去十年中，人们使用多种方法对两种主要的血小板 - 胶原蛋白受体——糖蛋白VI（GPVI）和整合素α(2)β(1)的作用进行了深入研究。在本研究中，我们采用药理学和遗传学方法研究了人和小鼠血小板在流动条件下对胶原蛋白的黏附。我们的研究表明，GPVI和整合素α(2)β(1)在血小板于流动状态下对胶原蛋白的黏附过程中都起着重要作用，并且两种受体的缺失会完全消除这种反应。由胞质衔接蛋白含Src同源2结构域的白细胞蛋白76 kDa（SLP - 76）介导的细胞内信号传导，而非由T细胞活化连接蛋白（LAT）介导的信号传导，对血小板在流动状态下对胶原蛋白的黏附至关重要。此外，GPVI受体密度降低会导致血小板在流动状态下对胶原蛋白的黏附出现严重缺陷。在流动状态下对胶原蛋白黏附的缺陷与缺乏一种或两种胶原蛋白受体的小鼠尾部出血时间延长有关。这些研究确定了在生理流动状态下血小板 - 胶原蛋白反应是两种结构不同的受体密切协作的结果，并表明这两种受体在体内都起着重要的止血作用。
The roles of the 2 major platelet-collagen receptors, glycoprotein VI (GPVI) and integrin alpha(2)beta(1), have been intensely investigated using a variety of methods over the past decade. In the present study, we have used pharmacologic and genetic approaches to study human and mouse platelet adhesion to collagen under flow conditions. Our studies demonstrate that both GPVI and integrin alpha(2)beta(1) play significant roles for platelet adhesion to collagen under flow and that the loss of both receptors completely ablates this response. Intracellular signaling mediated by the cytoplasmic adaptor Src homology 2 domain-containing leukocyte protein of 76 kDa (SLP-76) but not by the transmembrane adaptor linker for activation of T cells (LAT) is critical for platelet adhesion to collagen under flow. In addition, reduced GPVI receptor density results in severe defects in platelet adhesion to collagen under flow. Defective adhesion to collagen under flow is associated with prolonged tail-bleeding times in mice lacking one or both collagen receptors. These studies establish platelet-collagen responses under physiologic flow as the consequence of a close partnership between 2 structurally distinct receptors and suggest that both receptors play significant hemostatic roles in vivo.