ADP-dependent common receptor mechanism for binding of von Willebrand factor and fibrinogen to human platelets.
ADP-dependent common receptor mechanism for binding of von Willebrand factor and fibrinogen to human platelets.
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冯维勒布兰德因子和纤维蛋白原与人血小板结合的 ADP 依赖性共同受体机制。
DOI：
10.1073/pnas.81.15.4935
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发表时间：
1984
影响因子：
11.1
通讯作者：
Hawiger,J
中科院分区：
文献类型：
--
作者：
Timmons,S;Kloczewiak,M;Hawiger,J
人von Willebrand因子(VWF)和纤维蛋白原是形成血小板止血栓所必需的粘附性血浆糖蛋白。我们在体外研究了ADP和纤维蛋白原在vWF与血小板结合中的作用。经ADP处理后，125I标记的vWF与血浆蛋白分离的人血小板的结合是特异的，且具有时间和浓度依赖性，在20min达到平衡，在12微克/ml时接近饱和，这种结合可被EDTA和已知的血小板腺苷环化酶激活剂前列腺素I2抑制。一种嘌呤核苷酸亲和类似物5‘-对氟磺酰基苯甲酰腺苷(FSBA)，它共价修饰人血小板膜上的ADP结合部位，阻止了ADP诱导的vWF与人凝血酶和电离团A23187的结合，这些都是已知的导致血小板ADP分泌的试剂。相比之下，FSBA不能抑制瑞斯托菌素诱导的vWF结合，说明瑞斯托菌素的作用机制不依赖于ADP。人纤维蛋白原以竞争性方式抑制125I标记的vWF(9微克/毫升)与ADP诱导的结合，IC50为25微克/毫升。相反，未标记的vWF抑制ADP诱导的125I标记的纤维蛋白原(60微克/毫升)的结合，IC50为16微克/毫升。合成的十二肽(MR，1188)类似于人纤维蛋白原伽马链的血小板受体识别位点(Gamma 400-411)，可抑制125I标记的vWF和125I标记的纤维蛋白原与ADP处理的血小板的结合，而对125I标记的vWF与海洋黄素处理的血小板的结合没有影响。这些数据表明，vWF和纤维蛋白原与人血小板的相互作用具有共同的受体机制，该机制依赖于其结合部位的ADP占有率，并被人纤维蛋白原伽马链羧基末端的12个氨基酸残基序列识别。
Human von Willebrand factor (vWF) and fibrinogen are adhesive plasma glycoproteins essential for formation of a platelet hemostatic plug. We investigated the role of ADP and fibrinogen in binding of vWF to platelets in vitro. Binding of 125I-labeled vWF to human platelets separated from plasma proteins and treated with ADP was specific, and time and concentration dependent, reaching equilibrium at 20 min and approaching saturation at 12 micrograms/ml. The binding was inhibited by EDTA and by prostaglandin I2, a known activator of platelet adenylate cyclase. A purine nucleotide affinity analog, 5'-p-fluorosulfonylbenzoyl adenosine (FSBA), which covalently modifies the ADP binding sites on the human platelet membrane, prevented binding of vWF induced with ADP, as well as with human thrombin and with ionophore A23187, agents known to cause platelet ADP secretion. By comparison, FSBA did not inhibit binding of vWF induced by ristocetin, indicating that the ristocetin mechanism is not dependent on ADP. Human fibrinogen inhibited in a competitive manner the ADP-induced binding of 125I-labeled vWF (9 micrograms/ml) with an IC50 of 25 micrograms/ml. Conversely, unlabeled vWF inhibited ADP-induced binding of 125I-labeled fibrinogen (60 micrograms/ml) with an IC50 of 16 micrograms/ml. A synthetic dodecapeptide (Mr, 1188), analogous with the specific platelet receptor recognition site of human fibrinogen gamma chain (gamma 400-411), inhibited binding of both 125I-labeled vWF and 125I-labeled fibrinogen to ADP-treated platelets, whereas it was without effect on binding of 125I-labeled vWF to ristocetin-treated platelets. These data indicate that vWF and fibrinogen have a common receptor mechanism for their interaction with human platelets that is dependent on ADP occupancy of its binding sites and is recognized by the sequence of 12 amino acid residues at the carboxyl terminus of the human fibrinogen gamma chain.
与人纤维蛋白原γ链羧基末端片段上的人血小板受体相互作用的位点的定位。
DOI：
10.1016/0006-291x(82)91686-2
发表时间：
1982
影响因子：
3.1
作者：
Kloczewiak,M;Timmons,S;Hawiger,J
通讯作者：
Hawiger,J