Studies of factor Xa/phospholipid-induced intravascular coagulation in rabbits. Effects of immunodepletion of tissue factor pathway inhibitor.
Studies of factor Xa/phospholipid-induced intravascular coagulation in rabbits. Effects of immunodepletion of tissue factor pathway inhibitor.
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Xa 因子/磷脂诱导的兔血管内凝血的研究。
DOI：
10.1161/01.atv.13.11.1551
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Rapaport,SI
中科院分区：
文献类型：
--
作者：
Warn-Cramer,BJ;Rapaport,SI
在该实验室的早期研究中，获得了组织因子途径抑制物（TFPI）作为止血调节剂的生理功能的证据，该止血调节剂能够预防血栓形成并发症，否则血栓形成并发症可能由血液暴露于痕量组织因子（TF）引起。然而，不能得出TFPI的保护作用仅仅源于因子VIIa/TF催化活性的抑制的结论，因为TFPI在形成抑制的因子Xa/TFPI/因子VIIa/TF复合物中中和化学计量量的因子Xa。因此，我们研究了免疫耗竭TFPI对兔在TF不存在的情况下暴露于Xa因子和磷脂引起的凝血程度的影响。在一种实验方法中，因子Xa是在接受磷脂酰胆碱/磷脂酰丝氨酸（PCPS）囊泡输注的兔中用拉塞尔蝰蛇毒液的因子X活化级分（0.33微克/千克）内源性产生的，输注量为1毫克/千克，持续2小时。在第二种方法中，给兔子注射Xa因子（0.75微克/千克）和PCPS（12.5微克/千克）的复合物。与观察到的TFPI耗竭兔TF诱导的凝血致敏相反，TFPI耗竭兔不致敏凝血因子Xa和磷脂在TF的情况下启动。这些数据支持的结论，TFPI在调节TF依赖性凝血的生理功能主要源于其抑制因子VIIa/TF催化活性的能力。
In earlier studies from this laboratory evidence was obtained for a physiological function of tissue factor pathway inhibitor (TFPI) as a regulator of hemostasis capable of preventing thrombotic complications that might otherwise result from exposure of blood to trace amounts of tissue factor (TF). However, it was not possible to conclude that the protective effect of TFPI stemmed solely from inhibition of factor VIIa/TF catalytic activity, since TFPI neutralizes stoichiometric amounts of factor Xa in forming an inhibited factor Xa/TFPI/factor VIIa/TF complex. Therefore, we examined the effects of immunodepletion of TFPI on the extent of coagulation initiated in rabbits by exposure to factor Xa and phospholipid in the absence of TF. In one experimental approach, factor Xa was generated endogenously with the factor X-activating fraction of Russell's viper venom (0.33 microgram/kg) in rabbits receiving an infusion of phosphatidylcholine/phosphatidylserine (PCPS) vesicles, 1 mg/kg over 2 hours. In a second approach, rabbits were injected with a complex of factor Xa (0.75 microgram/kg) and PCPS (12.5 micrograms/kg). In contrast with the observed sensitization of TFPI-depleted rabbits to TF-induced coagulation, TFPI-depleted rabbits were not sensitized to coagulation initiated by factor Xa and phospholipid in the absence of TF. These data support the conclusion that the physiological function of TFPI in regulating TF-dependent coagulation stems primarily from its ability to inhibit factor VIIa/TF catalytic activity.