Chou Janet, Mackman Nigel, Merrill-Skoloff Glenn, Pedersen Brian, Furie Barbara C, Furie Bruce
Center for Hemostasis and Thrombosis Research, Vascular Biology Center, 330 Brookline Ave, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
Blood. 2004 Nov 15;104(10):3190-7. doi: 10.1182/blood-2004-03-0935. Epub 2004 Jul 27.
Tissue factor (TF) is expressed on nonvascular cells and cells within the vessel wall and circulates in blood associated with microparticles. Although blood-borne TF accumulates into the developing thrombus during thrombus formation, the contribution of blood-borne TF and vessel wall TF to thrombin generation in vivo following vessel injury is unknown. To determine the source and role of blood-borne microparticle TF, we studied arterial thrombus formation in a living mouse using intravital microscopy. Platelet, TF, and fibrin accumulation in the developing thrombus was compared in wild-type and low TF mice. Compared to wild-type mice, low TF mice formed very small platelet thrombi lacking TF or fibrin. Wild-type and low TF mice received transplants of bone marrow from wild-type and low TF mice. Arterial thrombi in low TF bone marrow/wild-type chimeric mice had decreased size and decreased TF and fibrin levels. Arterial thrombi in wild-type bone marrow/low TF chimeric mice showed decreased platelet thrombus size but normal TF and fibrin levels. This demonstrates that blood-borne TF associated with hematopoietic cell-derived microparticles contributes to thrombus propagation.
组织因子（TF）在非血管细胞和血管壁内的细胞上表达，并与微粒一起在血液中循环。尽管在血栓形成过程中，血源性TF会积聚到正在形成的血栓中，但血管损伤后，血源性TF和血管壁TF在体内对凝血酶生成的作用尚不清楚。为了确定血源性微粒TF的来源和作用，我们使用活体显微镜研究了活体小鼠的动脉血栓形成。比较了野生型和低TF小鼠在正在形成的血栓中血小板、TF和纤维蛋白的积聚情况。与野生型小鼠相比，低TF小鼠形成的血小板血栓非常小，缺乏TF或纤维蛋白。野生型和低TF小鼠接受了来自野生型和低TF小鼠的骨髓移植。低TF骨髓/野生型嵌合小鼠的动脉血栓大小减小，TF和纤维蛋白水平降低。野生型骨髓/低TF嵌合小鼠的动脉血栓显示血小板血栓大小减小，但TF和纤维蛋白水平正常。这表明与造血细胞衍生的微粒相关的血源性TF有助于血栓的扩展。
