Tissue factor: a mediator of inflammatory cell recruitment, tissue injury, and thrombus formation in experimental colitis.
Tissue factor: a mediator of inflammatory cell recruitment, tissue injury, and thrombus formation in experimental colitis.
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DOI：
10.1084/jem.20062354
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发表时间：
2007-07-09
期刊：
影响因子：
--
通讯作者：
Granger DN
中科院分区：
文献类型：
--
作者：
Anthoni C;Russell J;Wood KC;Stokes KY;Vowinkel T;Kirchhofer D;Granger DN
越来越多的证据表明，在急性和慢性炎症性疾病中，炎症和凝血途径之间存在相互作用。然而，目前尚不清楚凝血途径的成分，如组织因子（TF），是否有助于肠道炎症，以及靶向TF是否会减弱实验性结肠炎中发生的炎性细胞募集，组织损伤和增强血栓形成。给小鼠喂食3%葡聚糖硫酸钠（DSS）以诱导结肠炎症，其中一些小鼠接受小鼠TF阻断抗体（muTF-Ab）。在未治疗和muTF-Ab治疗的结肠炎小鼠中，监测了结肠小静脉中白细胞和血小板的粘附、提睾肌微血管中光/染料诱导的血栓形成、疾病活动指数、血浆中的凝血酶-抗凝血酶（达特）复合物以及结肠粘膜的组织病理学变化。在未经治疗的小鼠中，DSS引起结肠小静脉中粘附的白细胞和血小板的募集，引起大体和组织学损伤，增加血浆达特复合物，并增强肌肉小动脉中的血栓形成。在DSS结肠炎小鼠中，muTF-Ab防止达特复合物升高，减少血细胞募集和组织损伤，并钝化血栓形成。这些发现暗示TF在肠道炎症中，并支持实验性结肠炎中炎症和凝血之间的相互作用。
There is growing evidence for an interplay between inflammatory and coagulation pathways in acute and chronic inflammatory diseases. However, it remains unclear whether components of the coagulation pathway, such as tissue factor (TF), contribute to intestinal inflammation, and whether targeting TF will blunt the inflammatory cell recruitment, tissue injury, and enhanced thrombus formation that occur in experimental colitis. Mice were fed 3% dextran sodium sulfate (DSS) to induce colonic inflammation, with some mice receiving a mouse TF-blocking antibody (muTF-Ab). The adhesion of leukocytes and platelets in colonic venules, light/dye-induced thrombus formation in cremaster muscle microvessels, as well as disease activity index, thrombin–antithrombin (TAT) complexes in plasma, and histopathologic changes in the colonic mucosa were monitored in untreated and muTF-Ab–treated colitic mice. In untreated mice, DSS elicited the recruitment of adherent leukocytes and platelets in colonic venules, caused gross and histologic injury, increased plasma TAT complexes, and enhanced thrombus formation in muscle arterioles. muTF-Ab prevented elevation in TAT complexes, reduced blood cell recruitment and tissue injury, and blunted thrombus formation in DSS colitic mice. These findings implicate TF in intestinal inflammation and support an interaction between inflammation and coagulation in experimental colitis.