Blood-borne tissue factor:: Another view of thrombosis

Blood-borne tissue factor:: Another view of thrombosis
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DOI:
10.1073/pnas.96.5.2311
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发表时间:
1999-03-02
影响因子:
11.1
通讯作者:
Nemerson, Y
Nemerson, Y
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Giesen, PLA;Rauch, U;Nemerson, Y

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动脉血栓形成被认为是由血管壁上的组织因子(TF)与循环血液中的血小板和凝血因子相互作用引起的。根据这种模式,凝血是在血管受损和血液暴露于血管壁TF后开始的。我们研究了猪动脉介质(不含可染色TF)和暴露于流动的人类血液的胶原涂层玻璃载玻片(不含TF)上的血栓形成。在两种系统中,在5分钟灌注期间形成的血栓对TF染色强烈,其中大部分与细胞无关。抗TF抗体使猪动脉介质上形成的血栓数量减少了约70%,胶原涂层玻片上的血栓也减少了。沉积在载玻片上的TF是活跃的,因为血栓中有丰富的纤维蛋白,因子VIIal,一种有效的TF抑制剂,基本上消除了纤维蛋白的产生,并显着减少了血栓的质量,免疫电镜显示我们经常在血小板表面附近观察到TF阳性的膜囊泡。从健康受试者全血和血浆中提取因子X-a形成测定TF。免疫染色法检测外周血中含tf的中性粒细胞和单核细胞;我们的数据提出了白细胞是血液TF主要来源的可能性,我们认为血源性TF具有固有的血栓形成性,并可能参与血管损伤部位的血栓增殖。
Arterial thrombosis is considered to arise from the interaction of tissue factor (TF) in the vascular wall with platelets and coagulation factors in circulating blood. According to this paradigm, coagulation is initiated after a vessel is damaged and blood is exposed to vessel-wall TF, We have examined thrombus formation on pig arterial media (which contains no stainable TF) and on collagen-coated glass slides (which are devoid of TF) exposed to flowing native human blood. In both systems the thrombi that formed during a 5-min perfusion stained intensely for TF, much of which was not associated with cells. Antibodies against TF caused approximate to 70% reduction in the amount of thrombus formed on the pig arterial media and also reduced thrombi on the collagen-coated glass slides. TF deposited on the slides was active, as there was abundant fibrin in the thrombi, Factor VIIal, a potent inhibitor of TF, essentially abolished fibrin production and markedly reduced the mass of the thrombi, Immunoelectron microscopy revealed TF-positive membrane vesicles that we frequently observed in large clusters near the surface of platelets. TF, measured by factor X-a formation, was extracted from whole blood and plasma of healthy subjects. By using immunostaining, TF-containing neutrophils and monocytes were identified in peripheral blood; our data raise the possibility that leukocytes are the main source of blood TF, We suggest that blood-borne TF is inherently thrombogenic and may be involved in thrombus propagation at the site of vascular injury.