Inhibition of tissue factor limits the growth of venous thrombus in the rabbit
Inhibition of tissue factor limits the growth of venous thrombus in the rabbit
复制标题
DOI：
10.1046/j.1538-7836.2003.00110.x
复制
发表时间：
2003-05-01
影响因子：
10.4
通讯作者：
Riederer, MA
中科院分区：
文献类型：
--
作者：
Himber, J;Wohlgensinger, C;Riederer, MA
抗体介导的组织因子（TF）功能抑制在静脉剪切速率下在不含TF的表面上离体灌注人血液中减小血栓尺寸，表明TF可能参与深静脉血栓形成的机制。此外，在人离体形成的血栓和循环血液中鉴定了携带TF的单核细胞和多形核白细胞（PMN）白细胞。为了了解TF在血栓生长中的作用，我们应用了一种兔静脉血栓形成模型，其中在颈静脉或硅静脉分流器内安装了胶原涂层线。抑制性单克隆抗兔TF抗体（AP-1）或Napsaglitazone（凝血酶的特异性抑制剂）的作用通过连续监测I-125-纤维蛋白原掺入生长的血栓中来定量。用抗TF抗体获得的抗血栓形成效果与用凝血酶抑制剂萘沙佐米观察到的效果相当，表明在该动物模型中血栓传播是高度TF的。依赖。免疫染色显示TF主要与颈静脉或硅静脉分流中形成的血栓内的白细胞相关。胶原包被的盖玻片上的离体灌注实验证明了在循环血液中存在携带TF的PMN白细胞。结果表明，在家兔静脉血栓的生长是由凝块结合TF介导的，阻断TF活性可以抑制血栓的传播。
Antibody mediated inhibition of tissue factor (TF) function reduces thrombus size in ex vivo perfusion of human blood over a TF-free surface at venous shear rates suggesting that TF might be involved in the mechanism of deep vein thrombosis. Moreover, TF-bearing monocytes and polymorphonuclear (PMN) leukocytes were identified in human ex vivo formed thrombi and in circulating blood. To understand the role of TF in thrombus growth, we applied a rabbit venous thrombosis model in which a collagen-coated thread was installed within the jugular vein or within a silicon vein shunt. The effect of an inhibitory monoclonal antirabbit TF antibody (AP-1) or Napsagatran, a specific inhibitor of thrombin, was quantified by continuously monitoring I-125-fibrinogen incorporation into the growing thrombi. The antithrombotic effect obtained with the anti-TF antibody was comparable to the effect observed with the thrombin inhibitor napsagatran suggesting that in this animal model the thrombus propagation is highly TF. dependent. Immunostaining revealed that TF was mostly associated with leukocytes within the thrombi formed in the jugular vein or in the silicon vein shunt. Ex vivo perfusion experiments over collagen-coated coverslips demonstrated the presence of TF-bearing PMN leukocytes in circulating blood. The results suggest that in rabbits venous thrombus growth is mediated by clot-bound TF and that blocking the TF activity can inhibit thrombus propagation.