Rauch Bernhard Hermann
Institut für Pharmakologie, Abteilung Allgemeine Pharmakologie, Universitätsmedizin Greifswald, Ernst-Moritz-Arndt-Universität, Greifswald, Germany.
Cell Physiol Biochem. 2014;34(1):185-96. doi: 10.1159/000362994. Epub 2014 Jun 16.
Sphingosine 1-phosphate (S1P) is a multifunctional signaling lipid generated from sphingosine by sphingosine kinases. S1P formation has been shown in numerous cells in the circulation, including platelets, vascular endothelial and smooth muscle cells and monocytes. S1P also exerts multiple effects on these cells, i.e. cell proliferation and migration, activation of proinflammatory signaling pathways and release of additional inflammatory mediators. Similar activities and targets have also been identified for activated clotting factors such as thrombin or the activated factor-X (FXa), suggesting a possible involvement of S1P in thrombus-associated cellular signaling and thrombin-induced inflammatory reactions. Several levels of S1P-mediated, thrombin /FXa-induced signaling have already been identified: regulation of sphingosine kinase expression and activity, stimulation of S1P release from platelets and other cells and, possibly regulation of S1P-receptors on target cells. This review summarizes the current state of knowledge about S1P as a clotting factor-regulated molecular link between blood coagulation and inflammation. It is concluded that S1P might represent an until now underestimated lipid mediator of inflammatory reactions following activation of the clotting system and, in this context, also involved in the development and progression of atherosclerosis.
1-磷酸鞘氨醇（S1P）是一种由鞘氨醇激酶作用于鞘氨醇产生的多功能信号脂质。在循环系统的众多细胞中均已证实有S1P的生成，包括血小板、血管内皮细胞、平滑肌细胞和单核细胞。S1P对这些细胞也发挥多种作用，即细胞增殖与迁移、促炎信号通路的激活以及其他炎症介质的释放。对于凝血因子如凝血酶或活化的X因子（FXa）等活化形式，也已鉴定出类似的活性和作用靶点，这表明S1P可能参与血栓相关的细胞信号传导以及凝血酶诱导的炎症反应。现已确定了S1P介导的、凝血酶/FXa诱导的信号传导的几个层面：鞘氨醇激酶表达和活性的调节、血小板及其他细胞中S1P释放的刺激，以及可能对靶细胞上S1P受体的调节。本综述总结了目前关于S1P作为凝血因子调节的凝血与炎症之间分子联系的知识现状。得出的结论是，S1P可能代表一种迄今被低估的脂质介质，在凝血系统激活后引发炎症反应，在此背景下，也参与动脉粥样硬化的发生和发展。
