title: Platelet-derived sphingosine-1-phosphate and inflammation: from basic mechanisms to clinical implications.
abstract: 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.
authors.affiliation: a Department of Medical Biotechnology and Translational Medicine, LITA-Segrate , University of Milan , Milan , Italy.
authors.forename: Clara Di
authors.initials: CD
authors.lastname: Vito
authors.affiliation: a Department of Medical Biotechnology and Translational Medicine, LITA-Segrate , University of Milan , Milan , Italy.
authors.forename: Loubna Abdel
authors.initials: LA
authors.lastname: Hadi
authors.affiliation: b Neurosurgery Unit, Laboratory of Experimental Neurosurgery and Cell Therapy, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico , University of Milan , Milan , Italy.
authors.forename: Stefania Elena
authors.initials: SE
authors.lastname: Navone
authors.affiliation: b Neurosurgery Unit, Laboratory of Experimental Neurosurgery and Cell Therapy, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico , University of Milan , Milan , Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Marfia
authors.affiliation: c Division of Neurosurgery, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico , University of Milan , Milan , Italy.
authors.forename: Rolando
authors.initials: R
authors.lastname: Campanella
authors.affiliation: d Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico , Milan , Italy.
authors.forename: Maria Elisa
authors.initials: ME
authors.lastname: Mancuso
authors.affiliation: a Department of Medical Biotechnology and Translational Medicine, LITA-Segrate , University of Milan , Milan , Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Riboni
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D019898:Autocrine Communication; D001692:Biological Transport; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism; D008246:Lysophospholipids / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D015539:Platelet Activation; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism; D013927:Thrombosis / Q000097:blood / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D013110:Sphingosine
keywords: Inflammation; platelets; sphingosine-1-phosphate