Ambient particulate matter accelerates coagulation via an IL-6-dependent pathway
Ambient particulate matter accelerates coagulation via an IL-6-dependent pathway
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DOI：
10.1172/jci30639
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发表时间：
2007-10-01
影响因子：
15.9
通讯作者：
Budinger, G. R. Scott
中科院分区：
文献类型：
--
作者：
Mutlu, Goekhan M.;Green, David;Budinger, G. R. Scott
暴露在颗粒物中增加心血管事件风险的机制尚不清楚。最近的人类和动物数据表明，颗粒物可能会引起止血因素的变化。在这项研究中，我们确定了颗粒物可能加速血栓形成的机制。我们发现，用直径小于10微米的具有良好特性的颗粒物处理的小鼠，出血时间缩短，凝血酶原和部分凝血活酶时间减少(血浆凝血时间减少)，纤维蛋白原水平增加，凝血因子II、VIII和X的活性增加。这种血栓前倾向与血管内凝血酶的生成增加、动脉血栓形成加速以及支气管肺泡液中血栓前细胞因子IL-6的浓度增加有关。缺乏IL-6的基因敲除小鼠可以抵抗颗粒物质诱导的血管内凝血酶形成和动脉血栓形成的加速。通过气管内给药减少微粒物质诱导的IL-6的产生和由此导致的血栓前倾向来耗尽巨噬细胞。我们的发现表明，暴露在颗粒物中会触发肺泡巨噬细胞产生IL-6，导致凝血时间减少，血管内凝血酶形成，并加速动脉血栓形成。这些结果提供了环境颗粒物暴露和血栓形成事件之间的潜在机制。
The mechanisms by which exposure to particulate matter increases the risk of cardiovascular events are not known. Recent human and animal data suggest that particulate matter may induce alterations in hemostatic factors. In this study we determined the mechanisms by which particulate matter might accelerate thrombosis. We found that mice treated with a dose of well characterized particulate matter of less than 10 mu M in diameter exhibited a shortened bleeding time, decreased prothrombin and partial thromboplastin times (decreased plasma clotting times), increased levels of fibrinogen, and increased activity of factor II, VIII, and X. This prothrombotic tendency was associated with increased generation of intravascular thrombin, an acceleration of arterial thrombosis, and an increase in bronchoalveolar fluid concentration of the prothrombotic cytokine IL-6. Knockout mice lacking IL-6 were protected against particulate matter-induced intravascular thrombin formation and the acceleration of arterial thrombosis. Depletion of macrophages by the intratracheal administration of liposomal clodronate attenuated particulate matter-induced IL-6 production and the resultant prothrombotic tendency. Our findings suggest that exposure to particulate matter triggers IL-6 production by alveolar macrophages, resulting in reduced clotting times, intravascular thrombin formation, and accelerated arterial thrombosis. These results provide a potential mechanism linking ambient particulate matter exposure and thrombotic events.