Glycoprotein IIb-IIIa and RGD(S) are not important for fibronectin-dependent platelet adhesion under flow conditions.
Glycoprotein IIb-IIIa and RGD(S) are not important for fibronectin-dependent platelet adhesion under flow conditions.
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糖蛋白 IIb-IIIa 和 RGD(S) 对于流动条件下纤连蛋白依赖性血小板粘附并不重要。
DOI：
10.1182/blood.v72.1.82.82
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发表时间：
1988
期刊：
影响因子：
20.3
通讯作者：
J. Sixma
中科院分区：
文献类型：
--
作者：
P. Nievelstein;J. Sixma
以前的研究表明，活化的血小板通过纤维连接蛋白与糖蛋白IIb-IIIa复合体(GPIIb-IIIa)的结合而与纤维连接蛋白相互作用。纤维连接蛋白的细胞附着部位及其关键的Arg-Gly-asp(-Ser)[RGD(S)]序列参与了这些结合。我们研究了这些相互作用在流动条件下对纤维连接蛋白依赖的血小板黏附的重要性。比较了含RGDS的六肽(GRGDSP)和非反应性控制肽(GRGESP)。GRGDSP多肽在0.1 mmol/L的静态条件下抑制凝血酶诱导的聚集和黏附，该浓度对流动中血小板与非纤维性I型胶原的黏附没有影响。1 mmol/L的GRGDSP对1,500 S-1有明显的抑制作用，但在切变率较低的800和300 S-1时则无明显抑制作用，后者的血小板黏附也依赖于纤维连接蛋白。在培养的人脐静脉内皮细胞基质上，1 mmol/L GRGDSP对血小板黏附无影响。以内皮细胞基质(ECM)为表面，用抗GPIIb-IIIa的单抗和Glanzmann‘s血栓形成症患者的血小板研究了GPIIb-IIIa与纤维连接蛋白依赖性的关系。正常对照组或Glanzmann‘s血栓减少症患者的血小板在无纤维连接蛋白血浆的存在下，在ECM与抗纤维连接蛋白F(ab’)2片段预先孵育后，显示出类似的粘附性抑制。与抗GPIIb-IIIa孵育的血小板在高切变率下显示出抑制血小板黏附的作用。尽管单独的实验表明这些抗GPIIb-IIIa抗体可以阻断放射性标记的纤维连接蛋白与凝血酶激活的血小板的结合，但仍然观察到对纤维连接蛋白对血小板黏附的依赖。这些数据表明，存在另一种血小板与纤维连接蛋白相互作用的结合系统，只有当纤维连接蛋白存在于表面时才可能出现这种结合系统。
Previous studies have indicated that activated blood platelets interact with fibronectin through binding of fibronectin to the glycoprotein IIb-IIIa complex (GPIIb-IIIa). The cell attachment site of fibronectin with its crucial arg-gly-asp(-ser) [RGD(S)]sequence is involved in these bindings. We studied the importance of these interactions for the fibronectin dependence of platelet adhesion under flow conditions. An RGDS-containing hexapeptide (GRGDSP) was compared with a nonreactive control peptide (GRGESP). The GRGDSP-peptide inhibited thrombin-induced aggregation and adhesion under static conditions at 0.1 mmol/L. This concentration had no effect on platelet adhesion to nonfibrillar collagen type I in flow. GRGDSP at 1 mmol/L had a significant inhibitory effect at 1,500 s-1, but not at the lower shear rates of 800 and 300 s-1 where platelet adhesion is also fibronectin dependent. On the matrix of cultured human umbilical vein endothelial cells, 1 mmol/L GRGDSP had no effect on platelet adhesion. The relation between GPIIb-IIIa and fibronectin dependence was investigated with platelets of a patient with Glanzmann's thrombasthenia and monoclonal antibodies to GPIIb-IIIa using endothelial cell matrix (ECM) as a surface. Platelets of normal controls or a patient with Glanzmann's thrombasthenia showed a similar inhibition of adhesion in the presence of fibronectin-free plasma after the ECMs had been preincubated with antifibronectin F(ab')2 fragments. Incubation of platelets with anti-GPIIb-IIIa showed inhibition of platelet adhesion at high shear rates. Dependence on fibronectin for platelet adhesion was still observed even though separate experiments had shown that these anti-GPIIb-IIIa antibodies could block binding of radiolabeled fibronectin to thrombin-activated platelets. These data suggest the existence of another binding system for the interaction of platelets with fibronectin that may only appear when fibronectin is present on a surface.