Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
FASEB J. 2006 Oct;20(12):2118-20. Epub 2006 Aug 15.

Hydrogen sulfide is an endogenous modulator of leukocyte-mediated inflammation.

Author information

  • 1Inflammation Research Network, University of Calgary, Calgary, Alberta, Canada.

Abstract

Hydrogen sulfide (H2S) is increasingly recognized as an important signaling molecule in the cardiovascular and nervous systems. Recently, H2S donors were reported to induce neutrophil apoptosis and to suppress expression of some leukocyte and endothelial adhesion molecules. Using rats, we examined the possibility that H2S is an endogenous regulator of key inflammatory events at the leukocyte-endothelial interface. Via intravital microscopy, we observed that H2S donors (NaHS and Na2S) inhibited aspirin-induced leukocyte adherence in mesenteric venules (ED50 of 5.0 micromol/kg for Na2S), likely via activation of ATP-sensitive K+ (K(ATP)) channels. Inhibition of endogenous H2S synthesis elicited leukocyte adherence. Leukocyte infiltration in an air pouch model was also suppressed by H2S donors (NaHS, Lawesson's reagent, and N-acetylcysteine; ED50 of 42.7, 1.3, and 29.9 micromol/kg, respectively) and exacerbated by inhibition of endogenous H2S synthesis. Carrageenan-induced paw edema was suppressed by H2S donors (NaHS and Na2S; ED50s of 35 and 28 micromol/kg, respectively) to the same extent as by diclofenac and enhanced by an inhibitor of H2S synthesis. Suppression of edema formation by H2S donors was mimicked by a K(ATP) channel agonist and reversed by an antagonist of this channel. These results suggest that endogenous H2S is an important mediator of acute inflammation, acting at the leukocyte-endothelium interface. These findings have important implications for anti-inflammatory drug development.

PMID:
16912151
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Write to the Help Desk