title: Oxidant injury to the alveolar epithelium: biochemical and pharmacologic studies.
abstract: This multifaceted study involved a combined biochemical and cellular analysis of oxidant metabolism by a lung cell at risk from injury by endogenous and environmental oxidants, the pulmonary alveolar type II epithelial cell. Within the framework of this study, a method was developed for effectively delivering antioxidant enzymes and alpha-tocopherol to the intracellular compartment of alveolar epithelial cells. Alveolar type II cells are key sources of pulmonary surfactant phospholipids and apoproteins and serve as progenitors of type I alveolar epithelium, thus playing an important role in the re-epithelialization of the lung alveolus after exposure to pulmonary oxidants. The type I and II pulmonary epithelium also play an essential collaborative role in maintaining the integrity of the air-blood barrier of the lung. Because of these critical properties of the alveolar epithelium and their recognized sensitivity to oxidant stress derived from diverse sources, such as activated inflammatory cells, hyperoxia, the environmental oxidants and nitrogen dioxide, and surgical procedures, such as cardiopulmonary bypass and lung transplantation, we endeavored to understand more about the oxidant metabolism and antioxidant pharmacology of these cells. In our experiments, we made the observation that loss of differentiated oxidant generation and antioxidant properties of type II cells occurs very rapidly in vitro. For example, we observed a 50% to 75% reduction in the specific activities of type II cell superoxide dismutase, catalase, and glutathione peroxidase, all critical scavengers of cell superoxide and hydrogen peroxide and key enzymes in the attenuation of hydroxyl radical formation. Although the differentiated characteristics of the type II cell antioxidant defenses changed in vitro, they may have become more reflective of type I alveolar epithelial cells. The type I cell is the most vulnerable for oxidant damage in the alveolus because of its large surface area and the possibility of a reduced antioxidant capacity compared to type II alveolar epithelium. In spite of this limitation, we were able to culture type II cells and study their adaptive and toxic responses to exogenously administered oxidant stress. We also observed that a significant source of self-generated oxidants in type II cells was the enzyme xanthine oxidase. Normal rates of oxidant production by this enzyme had an inhibitory effect on incorporation of biosynthetic precursors into surfactant phospholipids; these effects were eliminated by the xanthine oxidase inhibitor, allopurinol.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Anesthesiology, University of Alabama, Birmingham 35294.
authors.forename: B A
authors.initials: BA
authors.lastname: Freeman
authors.forename: P C
authors.initials: PC
authors.lastname: Panus
authors.forename: S
authors.initials: S
authors.lastname: Matalon
authors.forename: B J
authors.initials: BJ
authors.lastname: Buckley
authors.forename: R R
authors.initials: RR
authors.lastname: Baker
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000378:metabolism; D002374:Catalase / Q000008:administration & dosage; D002478:Cells, Cultured; D004247:DNA; D004337:Drug Carriers; D004847:Epithelial Cells; D007770:L-Lactate Dehydrogenase / Q000008:administration & dosage / Q000378:metabolism; D008081:Liposomes; D016877:Oxidants / Q000009:adverse effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000008:administration & dosage; D014810:Vitamin E / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D004337:Drug Carriers; D008081:Liposomes; D016877:Oxidants; D017382:Reactive Oxygen Species; D014810:Vitamin E; D004247:DNA; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase