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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Biomarkers / analysis
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Bronchoalveolar Lavage Fluid
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Cell Adhesion*
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Extracellular Fluid / enzymology*
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Female
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Gene Expression Regulation, Enzymologic
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Humans
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Intercellular Adhesion Molecule-1 / metabolism
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Lipopolysaccharides / pharmacology*
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Lung / enzymology
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Lung / physiopathology*
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Macrophages / cytology
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Macrophages / metabolism
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Neutrophils / drug effects
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Neutrophils / enzymology
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Neutrophils / immunology
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Neutrophils / metabolism
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Peroxidase / metabolism
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Phagocytes / cytology
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Phagocytes / metabolism
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Pneumonia / enzymology
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Pneumonia / etiology*
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Pneumonia / physiopathology
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Selectins / metabolism
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Superoxide Dismutase / metabolism
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Superoxide Dismutase / pharmacology*
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Tumor Necrosis Factor-alpha / metabolism
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Vascular Cell Adhesion Molecule-1 / metabolism
Substances
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Biomarkers
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Lipopolysaccharides
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RNA, Messenger
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Selectins
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Tumor Necrosis Factor-alpha
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Vascular Cell Adhesion Molecule-1
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Intercellular Adhesion Molecule-1
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Peroxidase
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Superoxide Dismutase