Modderman P W, Huisman H G, van Mourik J A, von dem Borne A E
Central Laboratory, the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
Thromb Haemost. 1988 Aug 30;60(1):68-74.
The platelet glycoprotein (GP) IIb/IIIa complex functions as the receptor for fibrinogen on activated platelets. The effects of two anti-GPIIb/IIIa monoclonal antibodies on platelet function were studied. These antibodies, 6C9 and C17, recognized different epitopes, which were exclusively present on the undissociated GPIIb/IIIa complex. Whereas C17 inhibited the binding of fibrinogen to platelets and platelet aggregation induced by adenosine diphosphate (ADP) or collagen, 6C9 caused irreversible aggregation of platelets, both in the presence and absence of extracellular fibrinogen. When incubated with unstirred (non-aggregating) platelets, 6C9 induced release of alpha and dense granule-constituents as well as binding of 125I-fibrinogen to platelets. The latter was evidently mediated in part by platelet-derived ADP, since it was inhibited to a large extent by apyrase, the ADP-hydrolyzing enzyme. F(ab')2 fragments of 6C9 did not induce platelet-release reactions but caused (slow) aggregation of platelets in the presence of extracellular fibrinogen. These results indicate that binding of an antibody to a specific site on the platelet GPIIb/IIIa complex may cause fibrinogen-mediated aggregation. The Fc part of the platelet-bound antibody appears to be involved in the induction of platelet release.
血小板糖蛋白（GP）IIb/IIIa复合物在活化血小板上作为纤维蛋白原的受体发挥作用。研究了两种抗GPIIb/IIIa单克隆抗体对血小板功能的影响。这两种抗体，6C9和C17，识别不同的表位，这些表位仅存在于未解离的GPIIb/IIIa复合物上。C17抑制纤维蛋白原与血小板的结合以及由二磷酸腺苷（ADP）或胶原诱导的血小板聚集，而6C9在有和没有细胞外纤维蛋白原的情况下均导致血小板不可逆聚集。当与未搅拌（不聚集）的血小板一起孵育时，6C9诱导α颗粒和致密颗粒成分的释放以及125I-纤维蛋白原与血小板的结合。后者显然部分由血小板衍生的ADP介导，因为它在很大程度上被ADP水解酶——腺苷三磷酸双磷酸酶抑制。6C9的F（ab'）2片段不诱导血小板释放反应，但在细胞外纤维蛋白原存在下引起（缓慢）血小板聚集。这些结果表明，抗体与血小板GPIIb/IIIa复合物上特定位点的结合可能导致纤维蛋白原介导的聚集。结合在血小板上的抗体的Fc部分似乎参与了血小板释放的诱导。
