title: Effects of oxygen metabolites on rat alveolar type II cell viability and surfactant metabolism.
abstract: Neutrophil-derived reactive oxygen metabolites have been implicated as one mechanism for the cellular injury in the adult respiratory distress syndrome. Previous studies have demonstrated that alveolar lung fluid of patients with adult respiratory distress syndrome has abnormal composition and surface active properties. To examine the effects of oxygen metabolites on the viability and metabolism of type II alveolar pneumocytes, the cellular source of surfactant, isolated rat type II pneumocytes were exposed to reactive oxygen metabolites generated by the enzymatic action of xanthine oxidase upon hypoxanthine. Utilizing a 51Cr release assay to detect cellular death, we found that oxygen metabolites were lethal to type II cells in a dose-dependent manner. To demonstrate that oxygen metabolites were responsible for the toxicity, we assessed the protective effects of catalase and superoxide dismutase, scavengers of hydrogen peroxide and the superoxide anion, respectively. At a xanthine oxidase concentration of 50 mU/ml, catalase reduced the percentage of 51Cr release from 58.9 +/- 3.1% (SEM) to 7.2 +/- 2.3% (p less than 0.0001), whereas superoxide dismutase was without protection (58.9 +/- 3.1% versus 54.2 +/- 1.8% (p greater than 0.05). To determine whether oxygen metabolites also impair surfactant metabolism, we measured the incorporation of [3H]palmitate into the surfactant component disaturated phosphatidylcholine by type II pneumocytes. We found that sublethal amounts of generated oxygen metabolites caused a progressive decrease in the amount of [3H]palmitate incorporated into disaturated phosphatidylcholine. For example, using a xanthine oxidase concentration of 5 mU/ml (which causes no increased 51Cr release), we found that [3H]palmitate incorporation into disaturated phosphatidylcholine fell from a control level of 3.53 +/- 0.22 X 10(5) to 0.66 +/- 0.10 X 10(5) dpm/10(6) cells/4 hours (p less than 0.0001). Both catalase and superoxide dismutase protected the [3H]palmitate incorporation of oxygen metabolite-exposed type II cells. We conclude that reactive oxygen metabolites are injurious to type II pneumocytes and may result in impaired surfactant synthesis even at sublethal doses. Thus, oxygen metabolites generated by stimulated phagocytic cells may be responsible in part for the decreased surfactant that has been observed in adult respiratory distress syndrome.
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor.
authors.forename: C
authors.initials: C
authors.lastname: Crim
authors.forename: R H
authors.initials: RH
authors.lastname: Simon
mesh_terms: D000818:Animals; D002374:Catalase / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology*; D007042:Hypoxanthines / Q000378:metabolism; D008297:Male; D010100:Oxygen / Q000378:metabolism*; D010168:Palmitates / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D014176:Protein Biosynthesis; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D013047:Specific Pathogen-Free Organisms; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism / Q000494:pharmacology*; D014969:Xanthine Oxidase / Q000378:metabolism
chemical_list: D007042:Hypoxanthines; D010168:Palmitates; D010713:Phosphatidylcholines; D011663:Pulmonary Surfactants; D013481:Superoxides; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D010100:Oxygen