Ceramide triggers Weibel-Palade body exocytosis

Rinky Bhatia, Kenji Matsushita, Munekazu Yamakuchi, Craig N. Morrell, Wangsen Cao, Charles J. Lowenstein

Research output: Contribution to journalArticle

Abstract

The sphingolipid ceramide mediates a variety of stress responses, including vascular inflammation and thrombosis. Activated endothelial cells release Weibel-Palade bodies, granules containing von Willebrand factor (vWF) and P-selectin, which induce leukocyte rolling and platelet adhesion and aggregation. We hypothesized that ceramide induces vascular inflammation and thrombosis in part by triggering Weibel-Palade body exocytosis. We added ceramide to human aortic endothelial cells and assayed Weibel-Palade body exocytosis by measuring the concentration of vWF released into the media. Exogenous ceramide induces vWF release from endothelial cells in a dose-dependent manner. Activators of endogenous ceramide production, neutral sphingomyelinase, or tumor necrosis factor-α also induce Weibel-Palade body exocytosis. We next studied NO effects on ceramide-induced Weibel-Palade body exocytosis because NO can inhibit vascular inflammation. The NO donor S-nitroso-N-acetylpenicillamine decreases ceramide-induced vWF release in a dose-dependent manner, whereas the NO synthase inhibitor S-nitro-L-arginine methyl ester increases ceramide-induced vWF release. In summary, our findings show that endogenous ceramide triggers Weibel-Palade body exocytosis, and that endogenous NO inhibits ceramide-induced exocytosis. These data suggest a novel mechanism by which ceramide induces vascular inflammation and thrombosis.

Original languageEnglish (US)
Pages (from-to)319-324
Number of pages6
JournalCirculation research
Volume95
Issue number3
DOIs
StatePublished - Aug 6 2004

Keywords

  • Endothelial cells
  • Granule
  • N-ethylmaleimide sensitive factor
  • Nitric oxide
  • Sphingomyelin

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Bhatia, R., Matsushita, K., Yamakuchi, M., Morrell, C. N., Cao, W., & Lowenstein, C. J. (2004). Ceramide triggers Weibel-Palade body exocytosis. Circulation research, 95(3), 319-324. https://doi.org/10.1161/01.RES.0000136519.84279.7a