title: Endogenous hydrogen sulfide regulates leukocyte trafficking in cecal ligation and puncture-induced sepsis.
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.
authors.affiliation: Department of Pharmacology, Centre for Life Sciences, National University of Singapore, 28 Medical Drive, Singapore 117456.
authors.forename: Huili
authors.initials: H
authors.lastname: Zhang
authors.forename: Liang
authors.initials: L
authors.lastname: Zhi
authors.forename: Shabbir M
authors.initials: SM
authors.lastname: Moochhala
authors.forename: Philip Keith
authors.initials: PK
authors.lastname: Moore
authors.forename: Madhav
authors.initials: M
authors.lastname: Bhatia
mesh_terms: D000480:Alkynes / Q000494:pharmacology; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000276:immunology; D054426:Chemokine CXCL2 / Q000096:biosynthesis / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D036904:Leukocyte Rolling / Q000187:drug effects / Q000276:immunology*; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008642:Mesenteric Veins / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009570:Nitriles / Q000494:pharmacology; D011014:Pneumonia / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D023063:Receptors, Interleukin-8B / Q000096:biosynthesis / Q000276:immunology; D018805:Sepsis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013440:Sulfides / Q000494:pharmacology; D013450:Sulfones / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D000480:Alkynes; D015815:Cell Adhesion Molecules; D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D016328:NF-kappa B; D009570:Nitriles; D023063:Receptors, Interleukin-8B; D013440:Sulfides; D013450:Sulfones; C009055:propargylglycine; C025451:sodium bisulfide; D005998:Glycine; D006862:Hydrogen Sulfide