Interactive role of nitric oxide and superoxide anion in neutrophil-mediated endothelial cell injury.
This study addresses the interactive role of nitric oxide (NO) and reactive oxygen intermediates (ROI) by direct quantitation of NO and superoxide (O2-) in human neutrophil (PMN)-endothelial cell (EC) co-culture during PMN-mediated EC injury. The results directly demonstrate an inverse correlation between NO and ROI levels in PMN-EC co-culture, which significantly alters the PMN-EC adhesion and PMN-mediated EC killing. N-formylmethionyl-leucyl-phenylalanine (fMLF)-stimulated PMN adhesion to cytokine-treated EC was decreased (> 25%) in the presence of S-nitroso-N-penicillamine, a NO donor. NO also inhibited EC killing by stimulated PMN, suggesting its cytoprotective role. In addition, a significant decrease in NO levels was observed in the PMN-EC co-culture compared with the EC cultured alone (422.45 +/- 35.76 vs. 800.79 +/- 41.69 pmol). The reduced NO levels were restored by the addition of superoxide dismutase, a scavenger of O2-, suggesting that PMN-derived O2- is involved in the neutralization of NO in the co-culture. The results indicate an inverse correlation between NO and O2- in PMN-EC interactions and suggest the need for a critical balance between these two radicals in the regulation of PMN-mediated tissue injury.
Kausalya
S
S
Department of Respiratory Research, Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA.
Nath
J
J
D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology / Q000276:immunology*; D009569:Nitric Oxide / Q000276:immunology* / Q000378:metabolism; D013481:Superoxides / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology; D014657:Vasculitis / Q000276:immunology*
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D009569:Nitric Oxide; D007371:Interferon-gamma