Von Willebrand factor in the vessel wall mediates platelet adherence.
Von Willebrand factor in the vessel wall mediates platelet adherence.
复制标题
血管壁中的冯维勒布兰德因子介导血小板粘附。
作者：
H. V. Stel;K. Sakariassen;P. D. Groot;J. A. V. Mourik;J. Sixma
一种针对von Willebrand因子VIII-von Willebrand因子（FVIII-vWF）片段（vWF）的单克隆抗体，可阻断利斯托司汀诱导的血小板聚集以及在利斯托司汀存在时FVIII-vWF与血小板的结合，抑制正常血流中存在的血小板对人动脉内皮下层的粘附。这种单克隆抗体，CLB-RAg 35，抑制血小板粘附作为剪切速率的函数。在低于500 s-1的剪切速率下，血小板粘附不受影响，但在更高的剪切速率下，血小板粘附逐渐被抑制，在2500 s-1时平均达到正常值的11%。间接免疫荧光法证实了CLB-RAg 35与血管内皮下vWF的反应性。用该抗体预处理正常血管壁可抑制严重纯合子血管性血友病患者和正常人血液中血小板的粘附。抑制作用依赖于剪切速率，在高剪切速率（2,500 s-1）下显著。通过向正常血液中添加越来越多的纯化FVIII-vWF，抑制作用逐渐被克服。这些数据表明，血管壁上存在的vWF对血小板粘附有明显的贡献。在高壁剪切速率下，血小板粘附几乎完全由血浆FVIII-vWF和血管壁上的vWF介导。在低壁剪切速率下（低于500 s-1），血小板粘附的发生与血浆中的FVIII-vWF和血管壁中的vWF无关。
A monoclonal antibody directed against the von Willebrand factor moiety (vWF) of factor VIII-von Willebrand factor (FVIII-vWF), which blocks ristocetin-induced platelet aggregation as well as the binding of FVIII-vWF to platelets in the presence of ristocetin, inhibited platelet adherence to human artery subendothelium when present in normal flowing blood. This monoclonal antibody, CLB-RAg 35, inhibited platelet adherence as a function of the shear rate. At wall shear rates below 500 s-1, platelet adherence was not affected, but at higher shear rates platelet adherence was gradually inhibited, reaching an average of 11% of the normal value at 2,500 s-1. Indirect immunofluorescence established the reactivity of CLB-RAg 35 with vWF present in artery subendothelium. Pretreatment of normal vessel walls with this antibody inhibited adherence of platelets in blood from a patient with severe homozygous von Willebrand's disease and in blood from normal individuals. The inhibition was shear-rate dependent and significant at high shear rates (2,500 s-1). By adding increasing amounts of purified FVIII-vWF to normal blood, the inhibition was gradually overcome. These data indicate that vWF present in the vessel wall contributes appreciably to platelet adherence. At high wall shear rates, platelet adherence is mediated virtually completely by both plasma FVIII-vWF and vWF in the vessel wall. At low wall shear rates (below 500 s-1), platelet adherence occurs independent of FVIII-vWF in plasma and vWF in the vessel wall.