title: The serpentine path to a novel mechanism-based inhibitor of acute inflammatory lung injury.
abstract: The Comroe lecture on which this review is based described my research path during the past 45 years, beginning with studies of oxidant stress (hyperoxia) and eventuating in the discovery of a synthetic inhibitor of phospholipase A2 activity (called MJ33) that prevents acute lung injury in mice exposed to lipopolysaccharide. In between were studies of lung ischemia, lung surfactant metabolism, the protein peroxiredoxin 6 and its phospholipase A2 activity, and mechanisms for NADPH oxidase activation. These seemingly unrelated research activities provided the nexus for identification of a novel target and a potentially novel therapeutic agent for prevention or treatment of acute lung injury.
authors.affiliation: Institute for Environmental Medicine and the Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania abf@mail.med.upenn.edu.
authors.forename: Aron B
authors.initials: AB
authors.lastname: Fisher
mesh_terms: D055371:Acute Lung Injury / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000503:physiopathology; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D054465:Peroxiredoxin VI / Q000378:metabolism; D054467:Phospholipases A2 / Q000378:metabolism
chemical_list: D054465:Peroxiredoxin VI; D019255:NADPH Oxidases; D054467:Phospholipases A2
keywords: MJ33; NADPH oxidase; oxidant stress; peroxiredoxin 6; phospholipase A2
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