Effects of OKM5, a monoclonal antibody to glycoprotein IV, on platelet aggregation and thrombospondin surface expression.
Effects of OKM5, a monoclonal antibody to glycoprotein IV, on platelet aggregation and thrombospondin surface expression.
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DOI：
10.1182/blood.v76.12.2501.2501
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发表时间：
1990-12
期刊：
影响因子：
20.3
通讯作者：
Martha L. Aiken;M. Ginsberg;V. Byers-Ward;E. Plow
中科院分区：
文献类型：
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作者：
Martha L. Aiken;M. Ginsberg;V. Byers-Ward;E. Plow
单克隆抗体OKM 5识别88-Kd单核细胞膜蛋白，也结合血小板膜蛋白GPIV（GPIIb，CD 36）。在这项研究中，我们发现OKM 5靶表位以每个血小板约12，000个拷贝存在，并且与抗体的相互作用对血小板功能具有刺激和抑制作用。在没有其他刺激的情况下，OKM 5诱导血小板聚集、分泌和纤维蛋白原受体的表达。这些刺激反应需要完整抗体，因为F（ab '）2片段没有活性，但阻断了完整抗体的刺激活性。与此相反，暴露于OKM 5的血小板，随后是另一个强刺激，如凝血酶导致纤维蛋白原，纤连蛋白和血管性血友病因子结合到细胞的显着抑制。当弱刺激，腺苷二磷酸，是第二个激动剂，这种效果没有注意到。在OKM 5浓度干扰纤维蛋白原结合凝血酶刺激的血小板的80%至90%，外源性血小板反应蛋白的血小板结合，或内源性血小板反应蛋白的表面表达不受影响。OKM 5对纤维蛋白原与凝血酶刺激的血小板结合的抑制作用与样品中大量血小板聚集体的形成有关。这些结果表明，OKM 5与其血小板上的靶抗原的相互作用可以引起细胞的多种功能反应。
The monoclonal antibody, OKM5, recognizes an 88-Kd monocyte membrane protein and also binds to the platelet membrane protein, GPIV (GPIIIb, CD36). In this study, we have found that the OKM5 target epitope is present at approximately 12,000 copies per platelet and that interaction with the antibody has both stimulatory and inhibitory effects on platelet function. In the absence of other stimuli, OKM5 induced platelet aggregation, secretion, and expression of fibrinogen receptors. These stimulatory responses required intact antibody as F(ab')2 fragments were not active but blocked the stimulatory activity of the intact antibody. In contrast, exposure of platelets to OKM5 followed by another strong stimulus such as thrombin resulted in a marked suppression of fibrinogen, fibronectin, and von Willebrand factor binding to the cells. This effect was not noted when a weak stimulus, adenosine diphosphate, was the second agonist. At OKM5 concentrations that interfered with fibrinogen binding to thrombin-stimulated platelets by 80% to 90%, platelet binding of exogenous thrombospondin, or surface expression of endogenous thrombospondin was not affected. The inhibitory effect of OKM5 on fibrinogen binding to thrombin-stimulated platelets was related to the formation of massive platelet aggregates in the samples. These results show that interaction of OKM5 with its target antigen on platelets can elicit diverse functional responses from the cells.