Sphingosine 1-phosphate activates Weibel-Palade body exocytosis

Kenji Matsushita, Craig N. Morrell, Charles J. Lowenstein

Research output: Contribution to journalArticle

Abstract

Sphingosine 1-phosphate (S1P) not only regulates angiogenesis, vascular permeability and vascular tone, but it also promotes vascular inflammation. However, the molecular basis for the proinflammatory effects of S1P is not understood. We now show that S1P activates endothelial cell exocytosis of Weibel-Palade bodies, releasing vasoactive substances capable of causing vascular thrombosis and inflammation. S1P triggers endothelial exocytosis in part through phospholipase C-γ signal transduction. However, S1P also modulates endothelial cell exocytosis by activating endothelial nitric oxide synthase production of nitric oxide, which inhibits exocytosis. Thus S1P plays a dual role in regulating endothelial exocytosis, triggering pathways that both promote and inhibit endothelial exocytosis. Regulation of endothelial exocytosis may explain part of the proinflammatory effects of S1P.

Original languageEnglish (US)
Pages (from-to)11483-11487
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number31
DOIs
StatePublished - Aug 3 2004

Keywords

  • Ceramide
  • Endothelial
  • Nitric oxide
  • Von Willebrand factor

ASJC Scopus subject areas

  • Genetics
  • General

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