Abstract
Reactive oxygen and nitrogen species such as superoxide and nitric oxide are released into the extracellular spaces by inflammatory and airway epithelial cells. These molecules may exacerbate lung injury after influenza virus pneumonia. We hypothesized that enhanced expression of extracellular superoxide dismutase (EC SOD) in mouse airways would attenuate the pathological effects of influenza pneumonia. We compared the pathogenic effects of a nonlethal primary infection with mouse-adapted Hong Kong influenza A/68 virus in transgenic (TG) EC SOD mice versus non-TG (wild-type) littermates. Compared with wild-type mice, EC SOD TG mice showed less lung injury and inflammation as measured by significant blunting of interferon-gamma induction, reduced cell count and total protein in bronchoalveolar lavage fluid, reduced levels of lung nitrite/nitrate nitrotyrosine, and markedly reduced lung pathology. These results demonstrate that enhancing EC SOD in the conducting and distal airways of the lung minimizes influenza-induced lung injury by both ameliorating inflammation and attenuating oxidative stress.
Publication types
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Animals
-
Antioxidants / metabolism
-
Biomarkers
-
Bronchoalveolar Lavage Fluid / chemistry
-
Bronchoalveolar Lavage Fluid / cytology
-
Bronchoalveolar Lavage Fluid / immunology
-
Cytokines / analysis
-
Female
-
Gene Expression Regulation, Enzymologic / immunology
-
Glutathione Disulfide / immunology
-
Glutathione Disulfide / metabolism
-
Humans
-
Influenza A virus*
-
Influenza, Human / immunology
-
Influenza, Human / metabolism*
-
Influenza, Human / pathology*
-
Lung / immunology
-
Lung / pathology
-
Lung / virology
-
Male
-
Mice
-
Mice, Transgenic
-
Nitrates / analysis
-
Nitric Oxide Synthase / genetics
-
Nitric Oxide Synthase / metabolism
-
Nitric Oxide Synthase Type II
-
Nitrites / analysis
-
Oxidative Stress / immunology
-
Pneumonia, Viral / immunology
-
Pneumonia, Viral / metabolism*
-
Pneumonia, Viral / pathology*
-
Pulmonary Edema / immunology
-
Pulmonary Edema / metabolism
-
Pulmonary Edema / pathology
-
RNA, Messenger / analysis
-
Superoxide Dismutase / genetics*
-
Thromboxane B2 / metabolism
-
Tyrosine / analogs & derivatives*
-
Tyrosine / biosynthesis
Substances
-
Antioxidants
-
Biomarkers
-
Cytokines
-
Nitrates
-
Nitrites
-
RNA, Messenger
-
3-nitrotyrosine
-
Tyrosine
-
Thromboxane B2
-
NOS2 protein, human
-
Nitric Oxide Synthase
-
Nitric Oxide Synthase Type II
-
Nos2 protein, mouse
-
Superoxide Dismutase
-
Glutathione Disulfide