PMID: 8604026Mar 1, 1996Paper

Ceramide selectively inhibits early events in the response of human neutrophils to tumor necrosis factor

Journal of Leukocyte Biology
M FuortesC Nathan

Abstract

Cell spreading and the respiratory burst of neutrophils responding to soluble, physiological agents and adherent to model biological surfaces are typically delayed in onset by 15 min or more. The lag period may be a physiologically important feature of the action of such agents on neutrophils in that it may allow for migration before secretion. However, the mechanism that interposes such a long delay between stimulus and response is unknown. Tumor necrosis factor alpha (TNF-alpha) mediates some of its actions by triggering sphingomyelinase to generate ceramide. In adherent human neutrophils, however, exogenous ceramide did not mimic TNF-alpha's ability to stimulate cell spreading, paxillin tyrosine phosphorylation, or the respiratory burst. On the contrary, ceramide suppressed each such response. Ceramide did so by extending the lag period in the cells' response to TNF-alpha. Ceramide extended the lag period whether it was added exogenously or generated endogenously by sphingomyelinase, and the effect was reversible. Remarkably, however, ceramide inhibited cell spreading or the respiratory burst only if added together with TNF-alpha or within the next few minutes. Neutrophils ignored ceramide if it was added later, even if the ...Continue Reading

Citations

Jun 1, 2000·Laboratory Investigation; a Journal of Technical Methods and Pathology·V Witko-SarsatL Halbwachs-Mecarelli
Apr 10, 2010·American Journal of Respiratory Cell and Molecular Biology·Robert G SitrinHoward R Petty
Sep 4, 2012·Journal of the American Society of Nephrology : JASN·Lise Halbwachs, Philippe Lesavre
Sep 25, 2008·Biochemical and Biophysical Research Communications·Karina Alves ToledoLise Halbwachs-Mecarelli

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