Oxidant-antioxidant imbalance in the experimental interstitial lung disease induced in sheep by visna-maedi virus.
Infection of sheep by visna-maedi virus causes an interstitial pneumonitis similar to that associated with human immunodeficiency virus type-1 (HIV-1). Visna-maedi virus infection of alveolar macrophages leads to their activation. In this study we determined whether an imbalance in oxidant-antioxidant activity may be involved in the pathogenesis of the disease. We investigated the spontaneous and phorbol myristate acetate (PMA)-induced release of hydrogen peroxide (H2O2), and the activities of superoxide dismutase and glutathione peroxidase in alveolar macrophages from lambs experimentally-infected with visna-maedi virus, and in ovine alveolar macrophages infected in vitro. Alveolar macrophages from lambs experimentally-infected in vivo exhibited normal spontaneous H2O2 release and had superoxide dismutase and glutathione peroxidase activities similar to those from control animals. In contrast, after in vitro stimulation with PMA the H2O2 production by macrophages from experimentally-infected lambs was significantly increased. Similarly, spontaneous and PMA-induced H2O2 production by in vitro infected macrophages was significantly increased as compared to controls. In conclusion, the increased capacity of alveolar macrophages infected with the human immunodeficiency virus type-1-related visna-maedi virus to release hydrogen peroxide on stimulation suggests an oxidant-antioxidant imbalance, which may contribute to the pathogenesis of the observed chronic interstitial pneumonitis.
Laboratoire d'Immunologie et de Biologie Pulmonaire, INSERM CJF 93-08, Lyon, France.
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V
Cottin
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Court-Fortune
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Crevon
J F
JF
Mornex
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D002478:Cells, Cultured; D005979:Glutathione Peroxidase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D008168:Lung / Q000473:pathology / Q000821:virology; D008262:Macrophage Activation; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000821:virology; D016877:Oxidants / Q000378:metabolism*; D011021:Pneumonia, Progressive Interstitial, of Sheep / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D012756:Sheep; D013482:Superoxide Dismutase / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014790:Visna-maedi virus / Q000502:physiology
D000975:Antioxidants; D016877:Oxidants; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D013755:Tetradecanoylphorbol Acetate