Shear-dependent functions of the interaction between soluble von Willebrand factor and platelet glycoprotein Ib in mural thrombus formation on a collagen surface.
Shear-dependent functions of the interaction between soluble von Willebrand factor and platelet glycoprotein Ib in mural thrombus formation on a collagen surface.
复制标题
可溶性血管性血友病因子和血小板糖蛋白 Ib 之间相互作用在胶原表面壁血栓形成中的剪切依赖性功能。
DOI：
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发表时间：
1999
影响因子：
2.1
通讯作者：
Akira Yoshioka
中科院分区：
文献类型：
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作者：
M. Sugimoto;S. Tsuji;M. Kuwahara;Hideto Matsui;Shigeki Miyata;Yoshihiro Fujimura;Akira Yoshioka
最近的血流研究已经明确地确立了血管性血血病因子（vWF）在血小板初始粘附中的作用，其中表面固定的vWF与血小板糖蛋白（GP） Ib的相互作用，特别是在高剪切速率下，导致流动的血小板在表面上的短暂捕获。这种相互作用被认为触发血小板GP IIb/IIIa的激活，导致不可逆的血小板粘附和随后的壁血栓生长。然而，vWF-GP - Ib相互作用在继发性血栓生长中的作用仍有待阐明。在这项研究中，使用全血流系统获得血栓形成过程的时间过程图像，该系统可以实时可视化荧光标记的血小板血栓形成。该系统在安装在荧光显微镜上的平行板流室中采用胶原涂层表面，然后进行计算机辅助图像分析。在用抗vwf抗体NMC-4预孵育的血液灌注中，阻断溶液中vWF-GP Ib相互作用，在高剪切速率（>或= 1210/s）下，既没有检测到原发性血小板粘附，也没有检测到胶原表面随后的血栓生长。此外，即使在初始血小板粘附正常发生的实验条件下，nmc -4处理的血液灌注在相同的高剪切速率下也显示出继发性血栓生长的明显缺陷。在低剪切速率（<或= 340/s）下血栓形成的整个过程不受vWF-GP Ib相互作用的特异性阻滞剂的影响。这些发现表明，除了表面固定的vWF与GP Ib在血小板粘附中的相互作用外，可溶性vWF与GP Ib的相互作用是高剪切速率选择性继发性血栓生长所必需的。
Recent flow studies have clearly established the function of von Willebrand factor (vWF) in initial platelet adhesion, in which the interaction of surface-immobilized vWF with platelet glycoprotein (GP) Ib, particularly at high shear rates, leads to the transient capture of flowing platelets onto the surface. This interaction is thought to trigger activation of platelet GP IIb/IIIa, leading to irreversible platelet adhesion and subsequent mural thrombus growth. The role of vWF-GP Ib interaction in secondary thrombus growth remains to be clarified, however. In this study, time-course images of the thrombus formation process were obtained using a whole blood flow system that allows real-time visualization of fluorescence-labeled platelet thrombus formation. The system employs a collagen-coated surface in a parallel plate flow chamber mounted on an epifluorescence microscope, which is then subjected to computer-assisted image analysis. In perfusion of blood preincubated with anti-vWF antibody NMC-4, which blocks the vWF-GP Ib interaction in solution, neither primary platelet adhesion nor subsequent thrombus growth on a collagen surface was detected at high shear rates (> or = 1210/s). In addition, even under experimental conditions in which initial platelet adhesion normally occurred, NMC-4-treated blood perfusion showed an apparent defect of secondary thrombus growth at the same high shear rates. The overall process of thrombus formation at low shear rates (< or = 340/s) was not affected by specific blockers of the vWF-GP Ib interaction. These findings indicate that, in addition to the interaction of surface-immobilized vWF with GP Ib in platelet adhesion, the interaction of soluble vWF with GP Ib is required for secondary thrombus growth selectively at high shear rates.