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Nussbaum, Claudia; Bannenberg, Sarah; Keul, Petra; Gräler, Markus H.; Gonçalves-de-Albuquerque, Cassiano F.; Korhonen, Hanna; von Wnuck Lipinski, Karin; Heusch, Gerd; de Castro Faria Neto, Hugo C.; Rohwedder, Ina; Göthert, Joachim R.; Prasad, Vysakh Pushpa; Haufe, Günter; Lange-Sperandio, Baerbel; Offermanns, Stefan; Sperandio, Markus; Levkau, Bodo

Sphingosine-1-phosphate receptor 3 promotes leukocyte rolling by mobilizing endothelial P-selectin

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  • Medientyp: E-Artikel
  • Titel: Sphingosine-1-phosphate receptor 3 promotes leukocyte rolling by mobilizing endothelial P-selectin
  • Beteiligte: Nussbaum, Claudia; Bannenberg, Sarah; Keul, Petra; Gräler, Markus H.; Gonçalves-de-Albuquerque, Cassiano F.; Korhonen, Hanna; von Wnuck Lipinski, Karin; Heusch, Gerd; de Castro Faria Neto, Hugo C.; Rohwedder, Ina; Göthert, Joachim R.; Prasad, Vysakh Pushpa; Haufe, Günter; Lange-Sperandio, Baerbel; Offermanns, Stefan; Sperandio, Markus; Levkau, Bodo
  • Erschienen: Springer Science and Business Media LLC, 2015
  • Erschienen in: Nature Communications
  • Sprache: Englisch
  • DOI: 10.1038/ncomms7416
  • ISSN: 2041-1723
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>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 (S1P<jats:sub>3</jats:sub>) and Gα<jats:sub>q</jats:sub>, PLCβ and Ca<jats:sup>2+</jats:sup>. Intra-arterial S1P administration increases leukocyte rolling, while S1P<jats:sub>3</jats:sub> deficiency or inhibition dramatically reduces it. Mast cells involved in triggering rolling also release S1P that mobilizes P-selectin through S1P<jats:sub>3</jats:sub>. Histamine and epinephrine require S1P<jats:sub>3</jats:sub> for full-scale effect accomplishing it by stimulating sphingosine kinase 1 (Sphk1). In a counter-regulatory manner, S1P<jats:sub>1</jats:sub> inhibits cAMP-stimulated Sphk1 and blocks rolling as observed in endothelial-specific <jats:italic>S1P</jats:italic><jats:sub><jats:italic>1</jats:italic></jats:sub><jats:sup>−/−</jats:sup> mice. In agreement with a dominant pro-rolling effect of S1P<jats:sub>3</jats:sub>, FTY720 inhibits rolling in control and <jats:italic>S1P</jats:italic><jats:sub><jats:italic>1</jats:italic></jats:sub><jats:sup>−/−</jats:sup> but not in <jats:italic>S1P</jats:italic><jats:sub><jats:italic>3</jats:italic></jats:sub><jats:sup><jats:italic>−/−</jats:italic></jats:sup> mice. Our findings identify S1P as a direct and indirect contributor to leukocyte rolling and characterize the receptors mediating its action.</jats:p>
  • Zugangsstatus: Freier Zugang