An endothelial cell-dependent pathway of coagulation.

An endothelial cell-dependent pathway of coagulation.
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内皮细胞依赖性凝血途径。

DOI:
10.1073/pnas.82.8.2523
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发表时间:
1985
影响因子:
11.1
通讯作者:
Kisiel,W
Kisiel,W
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Stern,D;Nawroth,P;Handley,D;Kisiel,W

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虽然内皮细胞被认为是抗血栓形成的,但内皮细胞最近被证明参与促凝反应。在这份报告中,培养的牛主动脉内皮细胞显示出以因子XIa开始的促凝途径,导致因子IX、VIII、X和凝血酶原的激活,最终导致纤维蛋白肽a从纤维蛋白原中分裂并形成纤维蛋白凝块。电镜研究表明,纤维蛋白链与内皮细胞密切相关。内毒素处理的内皮细胞具有组织因子活性,在VIIa、IX、VIII、X因子、凝血酶原和纤维蛋白原存在的情况下产生纤维蛋白肽A。在存在因子IX和VIII时,由因子VIIa和内皮细胞表达的组织因子对因子X的激活比不存在因子IX和VIII时大10倍。这表明,在受干扰的内皮细胞表面,因子IX和因子VIII在因子x的激活中确实起着重要作用。添加血小板(10(8)/ ml)可使单独存在内皮的凝血酶形成增加约15倍。在血小板存在的情况下,抗人因子V IgG降低了这种增强的凝血酶形成,表明来自血小板的因子V在凝血酶形成中起着重要作用。这些数据使我们提出内皮细胞可以积极参与促凝反应。虽然血小板可以通过这些内皮细胞依赖性反应增强凝血酶的形成,但内皮细胞本身可以导致细胞相关纤维蛋白凝块的形成。内毒素处理的内皮细胞提供了一个血栓形成状态的模型,提供组织因子来启动凝血和传播导致纤维蛋白形成的反应。这种内皮细胞依赖性途径提示因子VIII和IX的核心作用与其在止血中的重要性一致。
Although the endothelial cell is considered antithrombogenic, endothelium has recently been shown to participate in procoagulant reactions. In this report cultured bovine aortic endothelial cells are shown to propagate a procoagulant pathway starting with factor XIa, leading to activation of factors IX, VIII, X, and prothrombin, culminating in fibrinopeptide A cleavage from fibrinogen and formation of a fibrin clot. Electron microscopic studies demonstrated that fibrin strands are closely associated with the endothelial cells. Endotoxin-treated endothelial cells, having acquired tissue factor activity, generated fibrinopeptide A in the presence of factors VIIa, IX, VIII, X, prothrombin, and fibrinogen. Factor X activation by factor VIIa and tissue factor expressed by endothelial cells is 10 times greater in the presence of factors IX and VIII than in their absence. This indicates that on the perturbed endothelial cell surface, factors IX and VIII do have an important role in the activation of factor X. Addition of platelets (10(8) per ml) augmented thrombin formation seen in the presence of endothelium alone by about 15-fold. Anti-human factor V IgG decreased this enhanced thrombin formation in the presence of platelets, indicating that factor V from platelets was playing an important role in thrombin formation. These data lead us to propose that endothelial cells can actively participate in procoagulant reactions. Although platelets can augment thrombin formation by these endothelial cell-dependent reactions, endothelial cells alone can lead to formation of a cell-associated fibrin clot. The endotoxin-treated endothelial cell provides a model of the thrombotic state supplying tissue factor to initiate coagulation and propagating the reactions leading to fibrin formation. This endothelial cell-dependent pathway suggests a central role for factors VIII and IX consistent with their importance in hemostasis.
人纤维蛋白原 b β 链 NH2 末端的纤溶酶蛋白水解序列。
DOI: 10.1016/0003-2697(83)90116-1
发表时间: 1983
影响因子: 2.9
作者:
Koehn,JA;Hurlet-Jensen,A;Nossel,HL;Canfield,RE
通讯作者: Canfield,RE