The S1P/S1P2 axis controls T-cell infiltration in a mast cell-dependent mouse model of acute pulmonary inflammation

Abstract

Event Abstract Back to Event The S1P/S1P2 axis controls T-cell infiltration in a mast cell-dependent mouse model of acute pulmonary inflammation Megan M. Price1, Yves T. Falanga2, John J. Ryan2, Roger Sabbadini3, Sarah Spiegel1 and Carole A. Oskeritzian4* 1 Virginia Commonwealth University, Biochemistry and Molecular Biology, United States 2 Virginia Commonwealth University, Biology, United States 3 Lpath, Inc., United States 4 University of South Carolina School of Medicine, Pathology, Microbiology and Immunology, United States Mast cells promote allergic inflammation by first secreting vasoactive mediators, including histamine and sphingosine-1-phosphate (S1P). However, the pathophysiology of acute allergic inflammation and its molecular mechanisms still remain unclear. We show that preventing signaling through the type 2 receptor for S1P (S1PR2) on mast cells by neutralizing its ligand S1P with a highly selective antibody SphingomabTM improved many inflammatory features associated with antigen (Ag) exposure, including circulating levels of histamine and chemokines and lung mast cell degranulation. Moreover, kinetic studies revealed that T cells and a few macrophages were recruited very early around pulmonary blood vessels within minutes after Ag challenge. This newly discovered early T cell infiltration was accompanied with increased serum levels of RANTES/CCL-5 and suppressed in the absence of mast cells, S1PR2 or intact S1PR2 signaling. Optimal RANTES/CCL5 secretion by IgE/Ag-activated mast cells also required functional S1PR2. We propose that perturbing S1PR2 signaling in mast cells might constitute an effective therapeutic strategy to prevent early T cell infiltration associated with allergic inflammation and therefore its persistency. Acknowledgements Supported by NIH grants R01 AI50094 to SS and U19 AI077435 to SS and JJR and K01AR053186 and R01 AI095494 to CAO. Keywords: airway inflammation, allergy, Mast Cells, recruitment, T cells, Sphingosine-1-phosphate, sphingosine-1-phosphate receptor 2, CCL5, mouse model, acute inflammation, human mast cells Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Immune-mediated disease pathogenesis Citation: Price MM, Falanga YT, Ryan JJ, Sabbadini R, Spiegel S and Oskeritzian CA (2013). The S1P/S1P2 axis controls T-cell infiltration in a mast cell-dependent mouse model of acute pulmonary inflammation. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.01066 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 28 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Carole A Oskeritzian, University of South Carolina School of Medicine, Pathology, Microbiology and Immunology, Columbia, South Carolina, 29209, United States, Carole.Oskeritzian@uscmed.sc.edu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Megan M Price Yves T Falanga John J Ryan Roger Sabbadini Sarah Spiegel Carole A Oskeritzian Google Megan M Price Yves T Falanga John J Ryan Roger Sabbadini Sarah Spiegel Carole A Oskeritzian Google Scholar Megan M Price Yves T Falanga John J Ryan Roger Sabbadini Sarah Spiegel Carole A Oskeritzian PubMed Megan M Price Yves T Falanga John J Ryan Roger Sabbadini Sarah Spiegel Carole A Oskeritzian Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.