Nagai H, Handa M, Kawai Y, Watanabe K, Ikeda Y
Research and Development Center, Terumo Corp., Kanagawa, Japan.
Thromb Res. 1993 Sep 15;71(6):467-77. doi: 10.1016/0049-3848(93)90120-d.
We investigated the molecular mechanism(s) by which platelets adhere to an artificial surface exposed to plasma, using polystyrene microtiter plates pretreated with plasma. Washed platelets labelled with 51Cr were incubated with the plates under static conditions. Prostaglandin E1(PGE1) was added to the platelets to prevent platelet-platelet interactions. Adhesion required the presence of a divalent cation such as Mg++ or Ca++. Polyclonal anti-fibrinogen antibody inhibited adhesion by 70%. Polyclonal antibodies against fibronectin, vitronectin, von Willebrand's Factor, and the Fc portion of human IgG, had no effect on adhesion. Platelets adhered normally to a surface pretreated with plasma from a patient with severe von Willebrand's disease. No platelet adhesion occurred when the surface was pretreated with an afibrinogenemic plasma. Monoclonal antibodies against platelet membrane GPIIb-IIIa, potent inhibitors of ADP-induced fibrinogen binding to platelets, completely inhibited adhesion. Monoclonal antibodies against the GPIb alpha subunit and GPIc(VLA alpha 5) showed no inhibitory effects on adhesion. Platelets from a patient with Glanzmann's thrombasthenia (type I) did not adhere to the surface pretreated with normal plasma. These results suggest that plasma fibrinogen adsorbed onto the surface and that platelet membrane glycoprotein(GP)IIb-IIIa were responsible for adhesion in an activation-independent manner.
我们使用经血浆预处理的聚苯乙烯微量滴定板,研究了血小板黏附于暴露于血浆的人工表面的分子机制。将用51Cr标记的洗涤血小板在静态条件下与这些板一起孵育。向血小板中加入前列腺素E1(PGE1)以防止血小板-血小板相互作用。黏附需要二价阳离子如Mg++或Ca++的存在。多克隆抗纤维蛋白原抗体可抑制70%的黏附。针对纤连蛋白、玻连蛋白、血管性血友病因子和人IgG的Fc部分的多克隆抗体对黏附没有影响。血小板能正常黏附于来自重度血管性血友病患者的血浆预处理的表面。当表面用无纤维蛋白原血浆预处理时,未发生血小板黏附。针对血小板膜糖蛋白GPIIb-IIIa的单克隆抗体,是ADP诱导的纤维蛋白原与血小板结合的有效抑制剂,可完全抑制黏附。针对GPIbα亚基和GPIc(VLAα5)的单克隆抗体对黏附无抑制作用。来自Glanzmann血小板无力症(I型)患者的血小板不黏附于用正常血浆预处理的表面。这些结果表明,吸附在表面的血浆纤维蛋白原和血小板膜糖蛋白(GP)IIb-IIIa以非活化依赖的方式负责黏附。