Endenburg S C, Hantgan R R, Lindeboom-Blokzijl L, Lankhof H, Jerome W G, Lewis J C, Sixma J J, de Groot P G
Department of Haematology, University of Utrecht, The Netherlands.
Blood. 1995 Dec 1;86(11):4158-65.
Platelet adhesion to fibrin at high shear rates depends on both the glycoprotein (GP) IIb:IIIa complex and a secondary interaction between GPIb and von Willebrand factor (vWF). This alternative link between platelets and vWF in promoting platelet adhesion to fibrin has been examined in flowing whole blood with a rectangular perfusion chamber. Optimal adhesion required both platelets and vWF, as shown by the following observations. No binding of vWF could be detected when plasma was perfused over a fibrin surface or when coated fibrinogen was incubated with control plasma in an enzyme-linked immunosorbent assay. However, when platelets were present during perfusion, interactions between vWF and fibrin could be visualized with immunoelectron microscopy. Exposure of fibrin surfaces to normal plasma before perfusion with severe von Willebrand's disease blood did not compensate for the presence of plasma vWF necessary for adhesion. vWF mutants in which the GPIIb:IIIa binding site was mutated or the GPIb binding site was deleted showed that vWF only interacts with GPIb on platelets in supporting adhesion to fibrin and not with GPIIb:IIIa. Complementary results were obtained with specific monoclonal antibodies against vWF. Thus, vWF must first bind to platelets before it can interact with fibrin and promote platelet adhesion. Furthermore, only GPIb, but not GPIIb:IIIa is directly involved in this interaction of vWF with platelets.
在高剪切速率下，血小板与纤维蛋白的黏附取决于糖蛋白（GP）IIb:IIIa复合物以及GPIb与血管性血友病因子（vWF）之间的二级相互作用。利用矩形灌注室在流动的全血中研究了血小板与vWF之间这种促进血小板与纤维蛋白黏附的替代联系。如下观察结果表明，最佳黏附需要血小板和vWF两者。当血浆灌注在纤维蛋白表面时，或在酶联免疫吸附测定中用包被的纤维蛋白原与对照血浆孵育时，未检测到vWF的结合。然而，当灌注过程中有血小板存在时，可用免疫电子显微镜观察到vWF与纤维蛋白之间的相互作用。在用重度血管性血友病血液灌注之前，将纤维蛋白表面暴露于正常血浆中并不能弥补黏附所需血浆vWF的存在。GPIIb:IIIa结合位点发生突变或GPIb结合位点被删除的vWF突变体表明，vWF仅在支持与纤维蛋白黏附时与血小板上的GPIb相互作用，而不与GPIIb:IIIa相互作用。用针对vWF的特异性单克隆抗体获得了互补结果。因此，vWF必须首先与血小板结合，才能与纤维蛋白相互作用并促进血小板黏附。此外，只有GPIb，而不是GPIIb:IIIa直接参与vWF与血小板的这种相互作用。
