title: Extracellular superoxide dismutase attenuates lipopolysaccharide-induced neutrophilic inflammation.
abstract: Extracellular superoxide dismutase (EC-SOD) is an abundant antioxidant in the lung and vascular walls. Previous studies have shown that EC-SOD attenuates lung injury in a diverse variety of lung injury models. In this study, we examined the role of EC-SOD in mediating lipopolysaccharide (LPS)-induced lung inflammation. We found that LPS-induced neutrophilic lung inflammation was exaggerated in EC-SOD-deficient mice and diminished in mice that overexpressed EC-SOD specifically in the lung. Similar patterns were seen for bronchoalveolar lavage cytokines, such as tumor necrosis factor-alpha, keratinocyte-derived chemokines, and macrophage inflammatory protein-2 as well as expression of lung intercellular adhesion molecule-1, vascular cell adhesion molecule-1, endothelial cell selectin, and platelet selectin. In a macrophage cell line, EC-SOD inhibited LPS-induced macrophage cytokine release, but did not alter expression of intercellular adhesion molecules in endothelial cells. These results suggest that EC-SOD plays an important role in attenuating the inflammatory response in the lung most likely by decreasing release of proinflammatory cytokines from phagocytes.
authors.affiliation: National Jewish Medical and Research Center, K736a, 1400 Jackson Street, Denver, CO 80206, USA. BowlerR@njc.org
authors.forename: Russell P
authors.initials: RP
authors.lastname: Bowler
authors.forename: Mike
authors.initials: M
authors.lastname: Nicks
authors.forename: Karen
authors.initials: K
authors.lastname: Tran
authors.forename: Grant
authors.initials: G
authors.lastname: Tanner
authors.forename: Ling-Yi
authors.initials: LY
authors.lastname: Chang
authors.forename: Scott K
authors.initials: SK
authors.lastname: Young
authors.forename: G Scott
authors.initials: GS
authors.lastname: Worthen
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001992:Bronchoalveolar Lavage Fluid; D002448:Cell Adhesion; D045604:Extracellular Fluid / Q000201:enzymology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000201:enzymology / Q000503:physiopathology*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D010586:Phagocytes / Q000166:cytology / Q000378:metabolism; D011014:Pneumonia / Q000201:enzymology / Q000209:etiology* / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019087:Selectins / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D015415:Biomarkers; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D019087:Selectins; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase; D013482:Superoxide Dismutase