Tissue Factor on the Loose
Tissue Factor on the Loose
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DOI：
10.1055/s-2000-8456
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发表时间：
2000
影响因子：
5.7
通讯作者：
P. Giesen;Y. Nemerson
中科院分区：
文献类型：
--
作者：
P. Giesen;Y. Nemerson
组织因子（TF）和凝血因子VIIa的酶复合物通常被认为是凝血的引发剂。在动脉管腔损伤部位发生凝血，与血小板沉积一起，是动脉血栓形成的原因，这是西方社会死亡的主要原因。病理情况下，内膜、新生内膜和动脉粥样硬化斑块含有活性TF。因此，血栓形成的开始被认为是由于TF存在于病理改变的动脉壁。这种关于血栓形成的经典观点受到了挑战。在这篇文章中，我们回顾了在血管壁外的各种组织中，以细胞外形式，以加密形式，甚至在血浆中存在TF活性的证据。我们发现，在生长因子或细胞因子刺激后，培养的多种细胞中都有TF的表达。这种TF通常也存在于细胞外基质中，此外，我们在未破裂的平滑肌细胞外发现了潜伏的TF。冷冻解冻细胞或洗涤剂裂解可以激活这种TF。我们还在天然全血和血浆中发现TF活性。在体外灌注系统中，抑制这种循环TF可防止胶原涂层玻片上血栓的形成。此外，在大鼠主动脉损伤的血栓形成模型中，在损伤主动脉的内膜表面发现了TF。在流动室中测量TF活性，结果表明所有可测量的活性都是细胞外的。我们得出结论，血源性TF在血栓形成中起主要作用。循环中TF的加密可能是防止血栓形成的机制。或者，循环TF可能是活跃的，但低于开始凝血所需的阈值。
The enzymatic complex of tissue factor (TF) and the blood coagulation factor VIIa is generally considered to be the initiator of coagulation. Coagulation that occurs at the site of luminal injury to an artery is, along with platelet deposition, the cause of arterial thrombosis, which is the leading cause of death in Western society. Under pathological conditions the intima, the neointima and the atherosclerotic plaque contain active TF. Therefore the initiation of thrombosis is believed to be due to TF present in the wall of the pathologically changed artery. This classical view of thrombosis has been challenged. In this article we review the evidence for the presence of TF activity in various tissues outside the vessel wall, in extracellular form, in encrypted form, and even in plasma. We found TF expression in a variety of cells in culture after growth factor or cytokine stimulation. This TF was often also present in the extracellular matrix, and in addition we found latent TF on the outside of unbroken smooth muscle cells. Freeze-thawing the cells or detergent lysis could activate this TF. We also found TF activity in native whole blood and in plasma. Inhibition of this circulating TF prevented formation of thrombi on collagen-coated glass slides in an ex vivo perfusion system. Furthermore, in a thrombosis model in which rat aorta was injured, TF was found on the intimal surface of the injured aorta. TF activity was measured in a flow chamber, and it was shown that all measurable activity was extracellular. We conclude that blood-borne TF plays a major role in thrombosis. Encryption of TF present in circulation could be a mechanism that prevents thrombosis. Alternatively, circulating TF may be active but below the threshold required for the initiation of blood coagulation.