PLATELETS HAVE MORE THAN ONE BINDING-SITE FOR VONWILLEBRAND-FACTOR

PLATELETS HAVE MORE THAN ONE BINDING-SITE FOR VONWILLEBRAND-FACTOR
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DOI:
10.1172/jci110946
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发表时间:
1983-01-01
影响因子:
15.9
通讯作者:
MONTGOMERY, RR
MONTGOMERY, RR
中科院分区:
医学1区
文献类型:
--
作者:
RUGGERI, ZM;DEMARCO, L;MONTGOMERY, RR

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~(125)I-vWF与凝血酶、ADP和ADP +肾上腺素(EPI)刺激的血小板的结合是特异的、可饱和的和可逆的。活性血小板代谢和二价阳离子所需的结合诱导这些刺激,但不是由ristoclavin,这表明存在不同的机制参与的vWF-血小板相互作用。针对膜糖蛋白(GP)Ib表位的单克隆抗体对凝血酶或ADP + EPI联合刺激的125 I-vWF与正常血小板的结合没有影响,但完全阻断了瑞斯托菌素诱导的结合。凝血酶诱导的GPIb阻断血小板的结合是特异性的。血小板缺乏GPIb的Bernard-Soulier综合征2例患者凝血酶诱导的125 I-vWF结合增加,而不是减少。针对GPIIb/IIIa复合物的单克隆抗体对瑞斯托菌素诱导的125 I-vWF与正常血小板的结合没有影响,但阻断凝血酶和ADP + EPI诱导的结合。为了排除血小板Fc受体介导的作用,使用了针对人B细胞和单核细胞上存在的表位的单克隆IgG,但其在静息或刺激的血小板上不表达。它不影响任何刺激诱导的125 I-vWF结合。血小板具有> 1个vWF结合位点,并且它们可以被不同的刺激暴露。
The binding of 125I-von Willebrand factor (125I-vWF) to platelets stimulated by thrombin, ADP and a combination of ADP + epinephrine (EPI) is specific, saturable and reversible. Active platelet metabolism and divalent cations are required for binding induced by these stimuli, but not by ristocetin, suggesting the existence of different mechanisms involved in the vWF-platelet interaction. A monoclonal antibody directed against an epitope of membrane glycoprotein (GP) Ib had no effect on the binding of 125I-vWF to normal platelets stimulated by thrombin or a combination of ADP + EPI, but completely blocked ristocetin-induced binding. Binding induced by thrombin to GPIb-blocked platelets was specific. Thrombin-induced binding of 125I-vWF was increased, rather than decreased, in 2 patients with the Bernard-Soulier syndrome whose platelets lacked GPIb. Monoclonal antibodies directed against the GPIIb/IIIa complex had no effect on ristocetin-induced binding of 125I-vWF to normal platelets, but blocked thrombin- and ADP + EPI-induced binding. To exclude effects mediated by the platelet Fc receptor, a monoclonal IgG directed against an epitope present on human B cells and monocytes, but not expressed on resting or stimulated platelets, was used. It did not affect 125I-vWF binding induced by any of the stimuli. Platelets have > 1 binding site for vWF, and they may be exposed by different stimuli.