EXPOSURE OF FIBRINOGEN RECEPTORS IN HUMAN-PLATELETS BY SURFACE PROTEOLYSIS WITH ELASTASE
EXPOSURE OF FIBRINOGEN RECEPTORS IN HUMAN-PLATELETS BY SURFACE PROTEOLYSIS WITH ELASTASE
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DOI：
10.1172/jci112370
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发表时间：
1986-03-01
影响因子：
15.9
通讯作者：
LENOX, RH
中科院分区：
文献类型：
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作者：
KORNECKI, E;EHRLICH, YH;LENOX, RH
用猪弹性蛋白酶预孵育的人血小板在加入纤维蛋白原后自发聚集。用浓度为111 μ g/ml的弹性蛋白酶预处理的血小板观察到对纤维蛋白原的最大聚集，并且在用11 μ g/ml弹性蛋白酶处理后发生半最大聚集。放射性标记的纤维蛋白原与弹性蛋白酶处理的血小板的结合是特异性的、可饱和的，并且显示48，400 ± 1的单一类别。每个血小板有9，697个纤维蛋白原结合位点，解离常数为6.30 ±。1.48. times. 10-7 M. ATP、腺苷三磷酸双磷酸酶和血小板腺苷酸环化酶的刺激剂forskolin、前列腺素E1、前列环素和N6，2“-O-二丁酰环腺苷酸不抑制纤维蛋白原诱导的弹性蛋白酶处理的血小板聚集。EDTA完全阻断了弹性蛋白酶处理的血小板聚集的起始，并逆转了纤维蛋白原诱导的血小板聚集。针对糖蛋白（GP）IIb和IIIa的单克隆和多克隆抗体完全阻断了纤维蛋白原诱导的弹性蛋白酶处理的血小板聚集。与这些抗体的免疫沉淀从表面放射性标记的，完整的，和弹性蛋白酶处理的血小板含有糖蛋白IIb和IIIa的洗涤剂提取物。我们的结论是，低浓度的弹性蛋白酶的表面蛋白水解可以暴露与血小板表面上的GPIIb和GPIIIa相关的纤维蛋白原结合位点，导致在添加纤维蛋白原后自发聚集。这些发现可能与循环弹性蛋白酶水平升高患者中观察到的止血变化相关。
Human platelets that were preincubated with porcine elastase aggregated spontaneously upon the addition of fibrinogen. Maximal aggregation to fibrinogen was observed with platelets pretreated with an elastase concentration of 111 .mu.g/ml, and half-maximal aggregation occurred after treatment with 11 .mu.g/ml elastase. Binding of radiolabeled fibrinogen to elastase-treated platelets was specific, saturable, and showed a single class of 48,400 .+-. 9,697 fibrinogen-binding sites per platelet with a dissociation constant of 6.30 .+-. 1.48 .times. 10-7 M. ATP, apyrase, and the stimulators of platelet adenylate cyclase forskolin, prostaglandin E1, prostacyclin, and N6,2''-O-dibutyryl cyclic AMP did not inhibit the fibrinogen-induced aggregation of elastase-treated platelets. EDTA completely blocked the initiation of aggregation and reversed the fibrinogen-induced aggregation of elastase-treated platelets. Monoclonal and polyclonal antibodies directed against glycoproteins (GP) IIb and IIIa completely blocked the fibrinogen-induced aggregation of elastase-treated platelets. Immunoprecipitates with these antibodies obtained from detergent extracts of surface-radiolabeled, intact, and elastase-treated platelets contained the glycoproteins IIb and IIIa. We conclude that surface proteolysis by low concentrations of elastase can expose fibrinogen-binding sites associated with GPIIb and GPIIIa on the platelet surface, resulting in spontaneous aggregation upon the addition of fibrinogen. These findings may be relevant to hemostatic changes observed in patients with increased levels of circulating elastase.