The role of carrier number on the procoagulant activity of tissue factor in blood and plasma.

The role of carrier number on the procoagulant activity of tissue factor in blood and plasma.
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DOI:
10.1088/1478-3975/8/6/066005
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发表时间:
2011-12
期刊:
影响因子:
2
通讯作者:
McCarty OJ
McCarty OJ
中科院分区:
生物学4区
文献类型:
--
作者:
Tormoen GW;Rugonyi S;Gruber A;McCarty OJ

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组织因子(TF)是活化凝血因子VII(FVIIa)的跨膜糖蛋白辅因子,在血管损伤部位产生止血凝血酶所需。在循环血液中也检测到的膜相关TF已被证明有助于局部血管损伤部位的实验性血栓传播。目前还不清楚TF如何在不引起血管内凝血的情况下循环。本研究旨在评估每单位体积TF诱导型单核细胞系U937或合成TF载体的载体数量是否影响促凝血活性,从而影响血栓形成潜力。进行实验以表征TF载体数量对开放和封闭系统中凝块形成动力学的影响。TF携带者的促凝血活性与携带者数量相关。TF载体增强了FVIIa对显色底物S-2366的酰胺分解活性,作为载体计数的函数。这些结果表明,TF启动凝血循环TF是动力学限制TF轴承表面之间的扩散路径长度。因此,循环TF的生物物理参数(如载体计数)和循环的流动参数是循环TF促凝血活性的关键决定因素。
Tissue factor (TF) is a transmembrane glycoprotein cofactor of activated blood coagulation factor VII (FVIIa) that is required for haemostatic thrombin generation at sites of blood vessel injury. Membrane-associated TF, also detected in circulating blood, has been shown to contribute to experimental thrombus propagation at sites of localized vessel injury. It remains uncertain how TF can circulate without initiating intravascular coagulation. This study was designed to assess whether the carrier number per unit volume of TF-inducible monocytic cell line U937 or synthetic TF-carriers affected procoagulant activity, hence thrombogenic potential. Experiments were performed to characterize the effects of TF-carrier number on the kinetics of clot formation in both open and closed systems. The procoagulant activity of TF carriers was found to correlate with carrier count. TF carriers enhanced the amidolytic activity of FVIIa towards the chromogenic substrate, S-2366, as a function of carrier count. These results suggest that TF-initiated coagulation by circulating TF is kinetically limited by diffusion path lengths between TF-bearing surface. Biophysical parameters of circulating TF such as carrier count, and flow parameters of the circulation are therefore critical determinants of the procoagulant activity of circulating TF.
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