Hematopoietic cell-derived microparticle tissue factor contributes to fibrin formation during thrombus propagation

Hematopoietic cell-derived microparticle tissue factor contributes to fibrin formation during thrombus propagation
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DOI:
10.1182/blood-2004-03-0935
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发表时间:
2004-11-15
期刊:
影响因子:
20.3
通讯作者:
Furie, B
Furie, B
中科院分区:
医学1区
文献类型:
--
作者:
Chou, J;Mackman, N;Furie, B

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组织因子 (TF) 在非血管细胞和血管壁内的细胞上表达,并在与微粒相关的血液中循环。尽管血源性 TF 在血栓形成过程中积累到正在形成的血栓中,但血源性 TF 和血管壁 TF 对血管损伤后体内凝血酶生成的贡献尚不清楚。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。比较野生型和低 TF 小鼠中正在形成的血栓中的血小板、TF 和纤维蛋白积累。与野生型小鼠相比,低TF小鼠形成非常小的缺乏TF或纤维蛋白的血小板血栓。野生型和低 TF 小鼠接受野生型和低 TF 小鼠的骨髓移植。低 TF 骨髓/野生型嵌合小鼠的动脉血栓尺寸减小,并且 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尺寸减小,但 TF 和纤维蛋白水平正常。这表明与造血细胞来源的微粒相关的血源性TF有助于血栓传播。 (C) 2004 年,美国血液学会。
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 bloodborne 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. (C) 2004 by The American Society of Hematology.