Vito Clara Di, Hadi Loubna Abdel, Navone Stefania Elena, Marfia Giovanni, Campanella Rolando, Mancuso Maria Elisa, Riboni Laura
a Department of Medical Biotechnology and Translational Medicine, LITA-Segrate , University of Milan , Milan , Italy.
b Neurosurgery Unit, Laboratory of Experimental Neurosurgery and Cell Therapy, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico , University of Milan , Milan , Italy.
Platelets. 2016 Jul;27(5):393-401. doi: 10.3109/09537104.2016.1144179. Epub 2016 Mar 7.
Beyond key functions in hemostasis and thrombosis, platelets are recognized as key players of inflammation, an underlying feature of a variety of diseases. In this regard, platelets act as a circulating source of several pro- and anti-inflammatory molecules, which are secreted from their intracellular stores upon activation. Among them, mounting evidence highlights a crucial role of sphingosine-1-phosphate (S1P), a multifunctional sphingoid mediator. S1P-induced pleiotropic effects include those crucial in inflammatory processes, such as the maintenance of the endothelial barrier integrity, and leukocyte activation and recruitment at the injured site. This review outlines the peculiar features and molecular mechanisms that allow platelets for acting as a unique factory that produces and stores S1P in large quantities. A particular emphasis is placed on the autocrine and paracrine roles of S1P derived from the "inflamed" platelets, highlighting the role of its cross-talk with endothelial and blood cells involved in inflammation, and the mechanisms of its contribution to the development and progression of inflammatory diseases. Finally, potential clinical implications of platelet-derived S1P as diagnostic tool of inflammatory severity, and as therapeutic target in inflammation are discussed.
除了在止血和血栓形成中的关键作用外，血小板还被认为是炎症的关键参与者，炎症是多种疾病的潜在特征。在这方面，血小板作为多种促炎和抗炎分子的循环来源，在激活后从其细胞内储存中分泌出来。其中，越来越多的证据突出了鞘氨醇-1-磷酸（S1P）这一多功能鞘脂介质的关键作用。S1P诱导的多效性作用包括在炎症过程中至关重要的作用，如维持内皮屏障完整性以及在损伤部位的白细胞激活和募集。本综述概述了使血小板能够作为大量产生和储存S1P的独特工厂的特殊特征和分子机制。特别强调了源自“炎症”血小板的S1P的自分泌和旁分泌作用，突出了其与参与炎症的内皮细胞和血细胞相互作用的作用，以及其对炎症性疾病发展和进展的贡献机制。最后，讨论了血小板衍生的S1P作为炎症严重程度诊断工具和炎症治疗靶点的潜在临床意义。
