Fibrinogen-independent platelet adhesion and thrombus formation on subendothelium mediated by glycoprotein IIb-IIIa complex at high shear rate.
Fibrinogen-independent platelet adhesion and thrombus formation on subendothelium mediated by glycoprotein IIb-IIIa complex at high shear rate.
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高剪切速率下糖蛋白 IIb-IIIa 复合物介导的不依赖纤维蛋白原的血小板粘附和内皮下血栓形成。
DOI：
10.1172/jci113871
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Hoffmann,T
中科院分区：
文献类型：
--
作者：
Weiss,HJ;Hawiger,J;Ruggeri,ZM;Turitto,VT;Thiagarajan,P;Hoffmann,T
在2,600 s-1的剪切速率下研究的内皮下血小板粘附和血栓形成被已知与GPIIb-IIIa相互作用的两种合成肽抑制。一种肽（HHLGGAKQAGDV）对应于纤维蛋白原γ链（γ 400-411）的羧基末端片段，另一种肽（RGDS）含有纤连蛋白、血管性血友病因子、玻连蛋白和纤维蛋白原α链共有的氨基酸序列Arg-Gly-Asp（RGD）。在患有严重先天性纤维蛋白原缺乏症的患者中，血小板粘附和血栓形成均未减少，并且当利用抗纤维蛋白原抗体进一步耗尽其血液中存在的少量纤维蛋白原时，情况同样如此。在正常受试者中，粘附和血栓形成被单克隆抗GPIIb-IIIa抗体（LJ-CP 8）的Fab'片段抑制，其干扰血小板与流体和固相中的所有四种粘附蛋白的相互作用。然而，另一种抗GPIIb-IIIa抗体（LJ-P5）对血小板与纤维蛋白原的相互作用具有最小的影响，但在不同程度上抑制血小板与其他粘附蛋白的相互作用，同样有效。研究结果表明，在2,600 s-1的剪切速率下，除纤维蛋白原外的粘附蛋白参与GPIIb-IIIa介导的血小板粘附和内皮下血栓形成。此外，由于LJ-P5抑制可溶性血管性血友病因子和玻连蛋白的结合，这些粘附蛋白可能参与血小板血栓形成。与在2，600 s-1剪切速率下获得的结果相反，纤维蛋白原可以在弱激动剂或较低剪切速率下介导血小板-血小板相互作用中发挥作用。
Platelet adhesion and thrombus formation on subendothelium, studied at a shear rate of 2,600 s-1, were inhibited by two synthetic peptides known to interact with GPIIb-IIIa. One peptide (HHLGGAKQAGDV) corresponds to the carboxyl terminal segment of the fibrinogen gamma-chain (gamma 400-411) and the other (RGDS) contains the amino acid sequence Arg-Gly-Asp (RGD) common to fibronectin, von Willebrand factor, vitronectin and the alpha-chain of fibrinogen. Neither platelet adhesion nor thrombus formation were decreased in a patient with severe congenital fibrinogen deficiency and this was equally true when his blood was further depleted of the small amounts of fibrinogen present utilizing an anti-fibrinogen antibody. In normal subjects, adhesion and thrombus formation were inhibited by the Fab' fragments of a monoclonal anti-GPIIb-IIIa antibody (LJ-CP8), which interferes with the interaction of platelets with all four adhesive proteins in both the fluid and solid phase. However, another anti-GPIIb-IIIa antibody (LJ-P5) that had minimal effects on the interaction of platelets with fibrinogen, but inhibited to varying degrees platelet interaction with other adhesive proteins, was equally effective. The findings demonstrate that, at a shear rate of 2,600 s-1, adhesive proteins other than fibrinogen are involved in GPIIb-IIIa-mediated platelet adhesion and thrombus formation on subendothelium. In addition, since LJ-P5 inhibited the binding of soluble von Willebrand factor and vitronectin, these adhesive proteins may be involved in platelet thrombus formation. In contrast to the results obtained at a shear rate of 2,600 s-1, fibrinogen could play a role in mediating platelet-platelet interactions with weak agonists or lower shear rates.
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DOI：
10.1016/s0021-9258(18)69172-0
发表时间：
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期刊：
The Journal of biological chemistry
影响因子：
--
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