title: Hyperbaric oxygen treatment reduces neutrophil-endothelial adhesion in chronic wound conditions through S-nitrosation.
abstract: Hyperbaric oxygen (HBO) therapy is an effective treatment for diabetic chronic wounds. HBO reduces inflammation and accelerates wound healing, by mechanisms that remain unclear. Here we examined a mechanism by which HBO may reduce neutrophil recruitment, through changes in endothelial and neutrophil adhesion molecule expression and function. Human umbilical vein endothelial cells and neutrophils were exposed to selected chronic wound conditions, comprising hypoxia in the presence of lipopolysaccharide and tumor necrosis factor-alpha, and then treated with HBO. We observed neutrophil adhesion to endothelial cells following treatment with chronic wound conditions, which was reversed by HBO treatment. This was partly explained by reduced expression of endothelial intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 by HBO. No changes in neutrophil adhesion molecule expression (CD18, CD11b, CD62L, CD31) were observed following HBO treatment. However, HBO decreased hydrogen peroxide generation by neutrophils, and induced nitrous oxide-related protein modifications. The transnitrosating agent S-nitroso-L-cysteine ethyl ester (600 μM) also reduced neutrophil adhesion to human umbilical vein endothelial cell monolayers, and the iNOS inhibitor 1400 W (10 μM) and HgCl2, which promotes the decomposition of S-nitrosothiols (1 mM), reversed the effect of HBO, suggesting that S-nitrosation may inhibit neutrophil-endothelial cell adhesion. This study indicates that HBO could reduce inflammation in wounds through reduced neutrophil recruitment, mediated by S-nitrosation.
authors.affiliation: Exeter University School of Medicine, Exeter, Devon, United Kingdom.
authors.forename: Alexandra C
authors.initials: AC
authors.lastname: Kendall
authors.forename: Jacqueline L
authors.initials: JL
authors.lastname: Whatmore
authors.forename: Paul G
authors.initials: PG
authors.lastname: Winyard
authors.forename: Gary R
authors.initials: GR
authors.lastname: Smerdon
authors.forename: Paul
authors.initials: P
authors.lastname: Eggleton
mesh_terms: D002448:Cell Adhesion; D002478:Cells, Cultured; D002908:Chronic Disease; D048909:Diabetes Complications / Q000276:immunology / Q000473:pathology* / Q000628:therapy; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D006931:Hyperbaric Oxygenation; D007249:Inflammation / Q000276:immunology / Q000473:pathology* / Q000628:therapy; D018836:Inflammation Mediators / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D015538:Nitrosation; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014456:Ulcer / Q000276:immunology / Q000473:pathology* / Q000628:therapy; D015854:Up-Regulation; D014945:Wound Healing
chemical_list: C508606:CXCL8 protein, human; D018836:Inflammation Mediators; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III