Chen D, Dorling A
Department of Immunology, Imperial College London, Hammersmith Hospital, London, UK.
J Thromb Haemost. 2009 Jul;7 Suppl 1:122-6. doi: 10.1111/j.1538-7836.2009.03413.x.
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.
凝血酶可通过多种方式放大由其他刺激诱导的炎症反应，这些方式包括：因血栓形成导致的缺血，通过生成下游介质（如活化蛋白C）间接放大炎症，或直接通过蛋白酶激活受体（PAR）发出的信号放大炎症。本文将总结我们实验室最近的数据，这些数据表明，凝血酶是启动CCR2依赖性白细胞募集所必需的，并且它是血管损伤后结果的主要决定因素，通过PAR-1激活平滑肌细胞祖细胞的一个独特亚群来发挥作用。在这两种情况下，组织因子（TF）启动凝血酶的生成，而凝血酶在局部起作用，这表明起始阶段可产生自分泌或旁分泌信号分子。凝血酶是固有免疫的重要组成部分，能够放大并调节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会促进创新抗炎策略的发展。
