Interactions of platelets with subendothelium and endothelium
Interactions of platelets with subendothelium and endothelium
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DOI：
10.1080/10739680590925484
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发表时间：
2005-04-01
期刊：
影响因子：
2.4
通讯作者：
López, KA
中科院分区：
文献类型：
--
作者：
Chen, JM;López, KA
本文就血小板在血管壁损伤时与内皮下的相互作用以及在炎症状态下与完整内皮的相互作用进行综述。当内皮下暴露于血管损伤后快速流动的血液时，血小板迅速粘附到暴露的表面，减速并聚集以阻止出血。在高剪切应力下，例如在微循环中发现的，需要内皮下血管性血友病因子（VWF）与其血小板受体糖蛋白（GP）Ib-IX-V之间的相互作用来减慢血小板并允许血小板胶原蛋白受体α 2 β 1和GP VI与胶原蛋白结合。GP VI和α 2 β 1在早期活化血小板中起重要作用，并与GP Ib-IX-V一起充分活化血小板以形成血栓。GP Ib-IX-V和GP VI采用类似的血小板活化信号传导途径，并且来自两种受体的信号被PECAM-1（血小板-内皮细胞粘附分子1）下调，以防止在高剪切下不必要的血小板活化。在炎症状态期间，完整的内皮细胞从它们的韦伯-帕拉德体释放VWF和P-选择素。这两种分子都是GP Ib-IX-V的配体。新释放的VWF比通常在血浆中发现的形式更大，更粘，并自发地结合血小板。通常，VWF通过血浆金属蛋白酶ADAMTS-13的蛋白水解进行加工。这个过程的失败导致微血管血栓性疾病血栓性血小板减少性紫癜。在这篇综述中，作者还使用血小板受体和配体的晶体结构来解释它们相互作用的细节。
In this review, the authors summarize how platelets interact with subendothelium when the vessel wall is damaged or with intact endothelium in the inflammatory state. When subendothelium is exposed to rapidly flowing blood upon vessel damage, platelets adhere rapidly to the exposed surface, decelerate, and aggregate to arrest bleeding. Under high shear stress, such as is found in the microcirculation, the interaction between subendothelial von Willebrand factor (VWF) and its platelet receptor, glycoprotein (GP) Ib-IX-V, is required to slow down platelets and allow the platelet collagen receptors alpha 2 beta 1 and GP VI to bind to collagen. GP VI and alpha 2 beta 1 play important roles to activate platelets in the early stage and work with GP Ib-IX-V to fully activate platelets to form thrombi. GP Ib-IX-V and GP VI employ similar signaling pathways for platelet activation and the signals from both receptors are down-modulated by PECAM-1 (platelet-endothelial-cell adhesion molecule 1) to prevent unnecessary platelet activation under high shear. During inflammatory states, intact endothelial cells release VWF and P-selectin from their Weibel-Palade bodies. Both molecules are ligands for GP Ib-IX-V. The newly released VWF is larger and stickier than the form normally found in plasma and binds platelets spontaneously. Normally, VWF is processed by proteolysis by the plasma metalloproteinase ADAMTS-13. Failure of this processing results in the microvascular thrombotic disorder thrombotic thrombocytopenic purpura. In this review, the authors also use available crystal structures of platelet receptors and ligands to explain the details of their interactions.