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Endogenous hydrogen sulfide regulates leukocyte trafficking in cecal ligation and puncture-induced sepsis.
- Source :
-
Journal of leukocyte biology [J Leukoc Biol] 2007 Oct; Vol. 82 (4), pp. 894-905. Date of Electronic Publication: 2007 Jun 28. - Publication Year :
- 2007
-
Abstract
- Hydrogen sulfide (H(2)S) is recognized increasingly as a proinflammatory mediator in various inflammatory conditions. Here, we have investigated the role of H(2)S in regulating expression of some endothelial adhesion molecules and recruitment of leukocytes to inflamed sites in sepsis. Male Swiss mice were subjected to cecal ligation and puncture (CLP)-induced sepsis and treated with saline (i.p.), DL-propargylglycine (PAG; 50 mg/kg, i.p.), an inhibitor of H(2)S formation or NaHS (10 mg/kg, i.p.), an H(2)S donor. PAG was administered 1 h before or after the induction of sepsis, and NaHS was given at the same time of CLP. Using intravital microcopy, we found that in sepsis, prophylactic and therapeutic administration of PAG reduced leukocyte rolling and adherence significantly in mesenteric venules coupled with decreased mRNA and protein levels of adhesion molecules (ICAM-1, P-selectin, and E-selectin) in lung and liver. In contrast, injection of NaHS up-regulated leukocyte rolling and attachment significantly, as well as tissue levels of adhesion molecules in sepsis. Conversely, normal mice were given NaHS (10 mg/kg, i.p.) to induce lung inflammation, with or without NF-kappaB inhibitor BAY 11-7082 pretreatment. NaHS treatment enhanced the level of adhesion molecules and neutrophil infiltration in lung. These alterations were reversed by pretreatment with BAY 11-7082. Moreover, expression of CXCR2 in neutrophils obtained from H(2)S-treated mice was up-regulated significantly, leading to an obvious elevation in MIP-2-directed migration of neutrophils. Therefore, H(2)S acts as an important endogenous regulator of leukocyte activation and trafficking during an inflammatory response.
- Subjects :
- Alkynes pharmacology
Animals
Cell Adhesion drug effects
Cell Adhesion immunology
Cell Adhesion Molecules biosynthesis
Cell Adhesion Molecules immunology
Chemokine CXCL2 biosynthesis
Chemokine CXCL2 immunology
Enzyme Inhibitors pharmacology
Glycine analogs & derivatives
Glycine pharmacology
Hydrogen Sulfide antagonists & inhibitors
Hydrogen Sulfide metabolism
Inflammation Mediators antagonists & inhibitors
Inflammation Mediators metabolism
Leukocyte Rolling drug effects
Liver immunology
Liver metabolism
Liver pathology
Lung immunology
Lung metabolism
Lung pathology
Male
Mesenteric Veins immunology
Mesenteric Veins metabolism
Mesenteric Veins pathology
Mice
NF-kappa B antagonists & inhibitors
NF-kappa B immunology
NF-kappa B metabolism
Neutrophil Infiltration drug effects
Neutrophils metabolism
Neutrophils pathology
Nitriles pharmacology
Pneumonia immunology
Pneumonia metabolism
Pneumonia pathology
Receptors, Interleukin-8B biosynthesis
Receptors, Interleukin-8B immunology
Sepsis metabolism
Sepsis pathology
Sulfides pharmacology
Sulfones pharmacology
Up-Regulation drug effects
Up-Regulation immunology
Hydrogen Sulfide immunology
Inflammation Mediators immunology
Leukocyte Rolling immunology
Neutrophil Infiltration immunology
Neutrophils immunology
Sepsis immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0741-5400
- Volume :
- 82
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of leukocyte biology
- Publication Type :
- Academic Journal
- Accession number :
- 17599903
- Full Text :
- https://doi.org/10.1189/jlb.0407237