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

Fingerprint

Weibel-Palade Bodies
Ceramides
Exocytosis
von Willebrand Factor
Blood Vessels
Inflammation
Thrombosis
Endothelial Cells
Leukocyte Rolling
S-Nitroso-N-Acetylpenicillamine
Sphingomyelin Phosphodiesterase
Sphingolipids
P-Selectin
Platelet Aggregation
Nitric Oxide Synthase

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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

Ceramide triggers Weibel-Palade body exocytosis. / Bhatia, Rinky; Matsushita, Kenji; Yamakuchi, Munekazu; Morrell, Craig N.; Cao, Wangsen; Lowenstein, Charles J.

In: Circulation Research, Vol. 95, No. 3, 06.08.2004, p. 319-324.

Research output: Contribution to journalArticle

Bhatia, R, Matsushita, K, Yamakuchi, M, Morrell, CN, Cao, W & Lowenstein, CJ 2004, 'Ceramide triggers Weibel-Palade body exocytosis', Circulation Research, vol. 95, no. 3, pp. 319-324. https://doi.org/10.1161/01.RES.0000136519.84279.7a
Bhatia R, Matsushita K, Yamakuchi M, Morrell CN, Cao W, Lowenstein CJ. Ceramide triggers Weibel-Palade body exocytosis. Circulation Research. 2004 Aug 6;95(3):319-324. https://doi.org/10.1161/01.RES.0000136519.84279.7a
Bhatia, Rinky ; Matsushita, Kenji ; Yamakuchi, Munekazu ; Morrell, Craig N. ; Cao, Wangsen ; Lowenstein, Charles J. / Ceramide triggers Weibel-Palade body exocytosis. In: Circulation Research. 2004 ; Vol. 95, No. 3. pp. 319-324.
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