Jackson S P, Nesbitt W S, Kulkarni S
Australian Center for Blood Diseases, Department of Medicine, Monash Medical School, Box Hill Hospital, Box Hill, Victoria, Australia.
J Thromb Haemost. 2003 Jul;1(7):1602-12. doi: 10.1046/j.1538-7836.2003.00267.x.
Recent in vivo studies have highlighted the dynamic and complex nature of platelet thrombus growth and the requirement for multiple adhesive receptor-ligand interactions in this process. In particular, the importance of von Willebrand factor (VWF) in promoting both primary adhesion and aggregation under high shear conditions is now well established. In general, the efficiency with which platelets adhere and aggregate at sites of vessel wall injury is dependent on the synergistic action of various adhesive and soluble agonist receptors, with the contribution of each of the individual receptors dependent on the prevailing blood flow conditions. In this review, we will discuss the major platelet adhesive interactions regulating platelet thrombus formation under high shear, with specific focus on the VWF (GPIb and integrin alphaIIbbeta3) and collagen receptors (GPVI and integrin alpha2beta1). We will also discuss the signaling mechanisms utilized by these receptors to induce platelet activation with specific emphasis on the role of cytosolic calcium flux in regulating platelet adhesion dynamics. The role of soluble agonists in promoting thrombus growth will be highlighted and a model to explain the synergistic requirement for adhesive and soluble stimuli for efficient platelet aggregation will be discussed.
最近的体内研究突出了血小板血栓形成的动态和复杂性质,以及在此过程中多种黏附受体 - 配体相互作用的必要性。特别是,血管性血友病因子(VWF)在高剪切条件下促进初始黏附和聚集方面的重要性现已得到充分证实。一般来说,血小板在血管壁损伤部位黏附和聚集的效率取决于各种黏附性和可溶性激动剂受体的协同作用,每个个体受体的贡献取决于当时的血流状况。在这篇综述中,我们将讨论在高剪切力下调节血小板血栓形成的主要血小板黏附相互作用,特别关注VWF(糖蛋白Ib和整合素αIIbβ3)和胶原受体(糖蛋白VI和整合素α2β1)。我们还将讨论这些受体用于诱导血小板活化的信号传导机制,特别强调胞质钙通量在调节血小板黏附动力学中的作用。将突出可溶性激动剂在促进血栓生长中的作用,并讨论一个解释黏附性和可溶性刺激对有效血小板聚集的协同需求的模型。