Oxygen toxicity: loss of lung macrophage function without metabolite depletion.
Hyperoxia inhibited concanavalin A stimulated O2- release (respiratory burst) of alveolar macrophages obtained by bronchoalveolar lavage from rats. After 36 h of normobaric 100% O2, a partial reversal (48%) of the inhibition was produced by addition of glucose. Since oxidant-induced, reversible NADPH depletion correlates with reversible inhibition of the respiratory burst, intracellular NADPH was assayed to determine whether irreversible inhibition of the respiratory burst was related to persistent changes in this metabolite. The cellular concentrations of ATP, glutathione, and ascorbate were also measured. After 36 h of hyperoxia, NADPH concentration in alveolar macrophages rose slightly while ATP and glutathione content remained at control levels. Ascorbate levels fell significantly but were not responsible for respiratory burst inhibition. Thus, irreversible loss of cellular function in hyperoxia is not due to persistent alterations in these metabolites. Significant amounts of both glutathione and ascorbate were found in extracellular fractions of lung washings, indicating high concentrations in the aqueous subphase in the lung fluid lining. There was no change in total content of these extracellular antioxidants following O2 exposure.
D000818:Animals; D001205:Ascorbic Acid / Q000032:analysis / Q000378:metabolism; D001980:Bronchi; D003208:Concanavalin A / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D005978:Glutathione / Q000032:analysis / Q000378:metabolism; D008168:Lung / Q000166:cytology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008297:Male; D009249:NADP / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology / Q000633:toxicity*; D011650:Pulmonary Alveoli / Q000166:cytology; D051381:Rats; D011919:Rats, Inbred Strains; D013481:Superoxides / Q000378:metabolism; D007507:Therapeutic Irrigation / Q000379:methods
D003208:Concanavalin A; D013481:Superoxides; D009249:NADP; D005978:Glutathione; D005947:Glucose; D001205:Ascorbic Acid; D010100:Oxygen