Critical roles for thrombin in acute and chronic inflammation
Critical roles for thrombin in acute and chronic inflammation
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DOI：
10.1111/j.1538-7836.2009.03413.x
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发表时间：
2009-07-01
影响因子：
10.4
通讯作者：
Dorling, A.
中科院分区：
文献类型：
--
作者：
Chen, D.;Dorling, A.
凝血酶可以通过缺血（血栓形成后）、间接通过下游介质（如活化蛋白 C）的产生或直接通过蛋白酶激活受体 (PAR) 的信号来放大其他刺激引起的炎症。本文将总结我们实验室的最新数据，表明凝血酶是启动 CCR2 依赖性白细胞招募所必需的，并且通过 PAR-1 激活平滑肌细胞祖细胞的独特子集，它是血管损伤后结果的主要决定因素。在这两种情况下，组织因子（TF）都会启动凝血酶的产生，并且凝血酶在局部发挥作用，这说明启动阶段可以产生自分泌或旁分泌信号分子。凝血酶是先天免疫的重要组成部分，能够放大和改变对入侵病原体或组织损伤的反应。随着新型抗凝血酶疗法和靶向 PAR 的药物的出现，对凝血酶重要性的新认识可能有助于开发创新的抗炎策略。
Thrombin can amplify inflammation induced by other stimuli, either through ischemia (consequent upon thrombosis), indirectly through generation of downstream mediators such as activated protein C, or directly via signals through protease activated receptors (PAR). This paper will summarize recent data from our laboratory indicating that thrombin is required to initiate CCR2-dependent leukocyte recruitment and that it is the principal determinant of the outcome after vascular injury, via PAR-1 activation of a distinct subset of smooth muscle cell progenitors. In both, tissue factor (TF) initiates thrombin generation and the thrombin acts locally, exemplifying that the initiation phase can generate autocrine or paracrine signalling molecules. Thrombin is an important constituent of innate immunity, able to amplify and modify responses to invading pathogens or tissue damage. With novel anti-thrombin therapeutics and agents to target PAR, a new understanding of the importance of thrombin may allow the development of innovative anti-inflammatory strategies.