Liposome-mediated augmentation of catalase in alveolar type II cells protects against H2O2 injury.
Oxidant injury to the alveolar epithelium can be mediated by exposure to oxidant gases such as O2 at high concentrations and O3, inflammatory cell-derived reactive O2 species, and the intracellular metabolism of xenobiotics such as paraquat. An in vitro model of alveolar epithelial oxidant injury was developed based on exposure of cultured rat type II pneumocytes to superoxide and hydrogen peroxide (H2O2) enzymatically generated in the culture medium. Cytotoxicity was assessed by the release of lactate dehydrogenase (LDH) into the culture medium, which was a more reliable indicator of damage than release of 51Cr by prelabeled cells. Incubation of cells for 6-8 h with xanthine plus xanthine oxidase and glucose plus glucose oxidase induced the release of greater than 50% of total intracellular LDH. Oxidant exposure also resulted in significant detachment of cells from culture dishes. Modulation of oxidant damage was accomplished using liposomes as vectors for the delivery of catalase. Treatment of cells with catalase liposomes for 2 h resulted in augmentation of cellular catalase specific activities up to 631% of controls. Catalase was partitioned into intracellular and surface-associated compartments in catalase liposome-treated cells. Partial and complete protection against oxidant injury, induced by xanthine plus xanthine oxidase and glucose plus glucose oxidase, respectively, was achieved by pretreatment of cells with catalase liposomes. LDH release during oxidant exposure was inversely related to augmentation of cellular catalase activities. Catalase liposome-treated cells also exhibited an enhanced ability to scavenge enzymatically generated H2O2 from the culture medium. These observations suggest a useful approach to modulation of alveolar injury induced by reactive O2 species.
D000818:Animals; D002374:Catalase / Q000494:pharmacology*; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006861:Hydrogen Peroxide / Q000633:toxicity*; D007545:Isoproterenol / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008081:Liposomes / Q000008:administration & dosage; D008297:Male; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000473:pathology*; D051381:Rats; D011919:Rats, Inbred Strains; D013481:Superoxides / Q000633:toxicity; D014969:Xanthine Oxidase / Q000494:pharmacology
D008081:Liposomes; D013481:Superoxides; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D014969:Xanthine Oxidase; D007545:Isoproterenol