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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Yearbook 2016     Display Documents



ID: 723949.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Yearbook 2016
Sphingosine-1-phosphate receptor 3 promotes leukocyte rolling by mobilizing endothelial P-selectin
Authors:Nussbaum, C.; Bannenberg, S.; Keul, P.; Graler, M. H.; Goncalves-de-Albuquerque, C. F.; Korhonen, H.; von Wnuck Lipinski, K.; Heusch, G.; de Castro Faria Neto, H. C.; Rohwedder, I.; Gothert, J. R.; Prasad, V. P.; Haufe, G.; Lange-Sperandio, B.; Offermanns, S.; Sperandio, M.; Levkau, B.
Date of Publication (YYYY-MM-DD):2015
Title of Journal:Nat Commun
Volume:6
Start Page:6416
Audience:Not Specified
Abstract / Description:Sphingosine-1-phosphate (S1P) participates in inflammation; however, its role in leukocyte rolling is still unclear. Here we use intravital microscopy in inflamed mouse cremaster muscle venules and human endothelial cells to show that S1P contributes to P-selectin-dependent leukocyte rolling through endothelial S1P receptor 3 (S1P3) and Galphaq, PLCbeta and Ca(2+). Intra-arterial S1P administration increases leukocyte rolling, while S1P3 deficiency or inhibition dramatically reduces it. Mast cells involved in triggering rolling also release S1P that mobilizes P-selectin through S1P3. Histamine and epinephrine require S1P3 for full-scale effect accomplishing it by stimulating sphingosine kinase 1 (Sphk1). In a counter-regulatory manner, S1P1 inhibits cAMP-stimulated Sphk1 and blocks rolling as observed in endothelial-specific S1P1(-/-) mice. In agreement with a dominant pro-rolling effect of S1P3, FTY720 inhibits rolling in control and S1P1(-/-) but not in S1P3(-/-) mice. Our findings identify S1P as a direct and indirect contributor to leukocyte rolling and characterize the receptors mediating its action.
External Publication Status:published
Document Type:Article
Communicated by:n.n.
Affiliations:MPI für physiologische und klinische Forschung
External Affiliations:Institute of Pathophysiology, West German Heart and Vascular Center, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany. Department of Anesthesiology and Intensive Care Medicine, Center for Sepsis Control and Care, Center for Molecular Biomedicine, University Hospital Jena, 07745 Jena, Germany. 1] Walter Brendel Center, Ludwig Maximilians Universitat Munchen, 81377 Munchen, Germany [2] Laboratorio de Imunofarmacologia, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040900, Brazil. Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany. Laboratorio de Imunofarmacologia, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040900, Brazil. Walter Brendel Center, Ludwig Maximilians Universitat Munchen, 81377 Munchen, Germany. Department of Hematology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany. Organisch-Chemisches Institut, Westfalische Wilhelms-Universitat Munster, 48149 Munster, Germany. Dr v. Haunersches Children's Hospital, Ludwig Maximilians University Munchen, 80337 Munchen, Germany.
Identifiers:ISSN:2041-1723 (Electronic) 2041-1723 (Linking) %R 10.1038/ncomms7416
URL:http://www.ncbi.nlm.nih.gov/pubmed/25832730
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