Savage B, Almus-Jacobs F, Ruggeri Z M
The Roon Research Center for Arteriosclerosis and Thrombosis, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA.
Cell. 1998 Sep 4;94(5):657-66. doi: 10.1016/s0092-8674(00)81607-4.
We have used confocal videomicroscopy in real time to delineate the adhesive interactions supporting platelet thrombus formation on biologically relevant surfaces. Type I collagen fibrils exposed to flowing blood adsorb von Willebrand factor (vWF), to which platelets become initially tethered with continuous surface translocation mediated by the membrane glycoprotein Ib alpha. This step is essential at high wall shear rates to allow subsequent irreversible adhesion and thrombus growth mediated by the integrins alpha2beta1 and alpha(IIb)beta3. On subendothelial matrix, endogenous vWF and adsorbed plasma vWF synergistically initiate platelet recruitment, and alpha2beta1 remains key along with alpha(IIb)beta3 for normal thrombus development at all but low shear rates. Thus, hemodynamic forces and substrate characteristics define the platelet adhesion pathways leading to thrombogenesis.
我们实时使用共聚焦视频显微镜来描绘在生物相关表面上支持血小板血栓形成的粘附相互作用。暴露于流动血液中的I型胶原纤维吸附血管性血友病因子（vWF），血小板最初通过膜糖蛋白Ibα介导的连续表面移位与vWF相连。在高壁剪切速率下，这一步骤对于随后由整合素α2β1和α（IIb）β3介导的不可逆粘附和血栓生长至关重要。在内皮下基质上，内源性vWF和吸附的血浆vWF协同启动血小板募集，除低剪切速率外，α2β1与α（IIb）β3一起对于正常血栓形成仍然至关重要。因此，血流动力学力和底物特性决定了导致血栓形成的血小板粘附途径。
