The tissue factor requirement in blood coagulation
The tissue factor requirement in blood coagulation
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DOI：
10.1074/jbc.m505506200
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发表时间：
2005-12-30
影响因子：
4.8
通讯作者：
Mann, KG
中科院分区：
文献类型：
--
作者：
Orfeo, T;Butenas, S;Mann, KG
当膜定位的组织因子（TF）暴露于血液时触发凝血酶的形成。在该过程的封闭模型中，凝血酶形成显示起始阶段（低速率的凝血酶产生引起血小板活化和纤维蛋白原凝血）、传播阶段（> 95%的凝血酶产生发生）和终止阶段（凝血酶原活化停止并且游离凝血酶失活）。目前的争议集中在TF刺激是否需要从血液TF循环池补充，以维持足够的促凝反应。我们已经评估了凝血反应进展期间对TF的需求，并将这些分析扩展到评估再补给（“血流置换”）期间对TF的需求。在起始阶段的不同时间TF活性的消除表明：绝对依赖期（< 10 s）;过渡期，其中对TF的依赖是部分的，并随着反应的进行而减少（10-240 s）;和一个时期，其中反应的进展是TF独立的（> 240 s）。在终止阶段后期，用新鲜反应物（但没有TF）再补给反应，产生了与原始传播阶段相似的凝血酶形成的立即爆发。我们的数据表明，独立于初始TF刺激是通过传播阶段的开始实现的，并且产生这种TF独立性的凝血产物和中间体的集合在相当长的时间内保持其凝血酶原激活潜力。这些观察结果支持的假设，即短暂的，局部表达的TF是足以维持TF独立的促凝反应，只要流量持续。
Formation of thrombin is triggered when membrane-localized tissue factor (TF) is exposed to blood. In closed models of this process, thrombin formation displays an initiation phase (low rates of thrombin production cause platelet activation and fibrinogen clotting), a propagation phase (> 95% of thrombin production occurs), and a termination phase (prothrombin activation ceases and free thrombin is inactivated). A current controversy centers on whether the TF stimulus requires supplementation from a circulating pool of blood TF to sustain an adequate procoagulant response. We have evaluated the requirement for TF during the progress of the blood coagulation reaction and have extended these analyses to assess the requirement for TF during resupply ("flow replacement"). Elimination of TF activity at various times during the initiation phase indicated: a period of absolute dependence (< 10 s); a transitional period in which the dependence on TF is partial and decreases as the reaction proceeds (10-240 s); and a period in which the progress of the reaction is TF independent (> 240 s). Resupply of reactions late during the termination phase with fresh reactants, but no TF, yielded immediate bursts of thrombin formation similar in magnitude to the original propagation phases. Our data show that independence from the initial TF stimulus is achieved by the onset of the propagation phase and that the ensemble of coagulation products and intermediates that yield this TF independence maintain their prothrombin activating potential for considerable time. These observations support the hypothesis that the transient, localized expression of TF is sufficient to sustain a TF-independent procoagulant response as long as flow persists.