Watts I S, Keery R J, Lumley P
Department of Cardiovascular Pharmacology, Glaxo Group Research Ltd, Ware, Hertfordshire, UK.
Thromb Haemost. 1989 Nov 24;62(3):955-61.
We have investigated the effect of two procedures that modify human platelet surface membrane glycoprotein (Gp) IIb and IIIa complexes upon whole blood platelet aggregation to a range of agonists. (A) Irreversible disruption of complexes by temporary (30 min) Ca2+-deprivation with EGTA at 37 degrees C. (B) Binding of a monoclonal antibody M148 to the complex. EGTA exposure abolished aggregation to ADP, adrenaline and PAF. In contrast, full aggregation curves to collagen and U-46619 could still be established. EGTA exposure reduced M148 binding to platelets by 80%. Excess M148 abolished aggregation to ADP, PAF, collagen and U-46619. However, upon removal of unbound antibody from platelets full aggregation curves to collagen and U-46619 but not to ADP and PAF could be re-established. Thus human platelet aggregation to ADP, PAF and adrenaline appears absolutely dependent upon surface membrane GpIIb/IIIa complexes. In contrast, collagen and U-46619 cause expression of an additional distinct pool of Gp complexes inaccessible to EGTA and M148 in unstimulated platelets which is intimately involved in aggregation to these agonists.
我们研究了两种改变人血小板表面膜糖蛋白（Gp）IIb和IIIa复合物的方法对全血血小板对一系列激动剂聚集的影响。（A）在37℃下用EGTA进行30分钟的短暂Ca2+剥夺对复合物进行不可逆破坏。（B）单克隆抗体M148与复合物的结合。EGTA处理消除了对ADP、肾上腺素和PAF的聚集。相反，对胶原和U-46619仍可建立完整的聚集曲线。EGTA处理使M148与血小板的结合减少了80%。过量的M148消除了对ADP、PAF、胶原和U-46619的聚集。然而，从血小板中去除未结合的抗体后，对胶原和U-46619（而非ADP和PAF）可重新建立完整的聚集曲线。因此，人血小板对ADP、PAF和肾上腺素的聚集似乎绝对依赖于表面膜GpIIb/IIIa复合物。相反，胶原和U-46619会导致在未刺激的血小板中出现一个额外的、EGTA和M148无法接近的独特Gp复合物池的表达，该池与对这些激动剂的聚集密切相关。
