Biochemical factors in pulmonary inflammatory disease.
Various biochemical events taking place during pulmonary inflammation were examined in the bronchoalveolar lavage (BAL) fluids from patients with acute respiratory distress syndrome (ARDS) and in experimental animal models. In patients with ARDS, active neutrophil elastase was found in the BAL fluids. In these fluids, inactivation of the major elastase inhibitor alpha 1-protease inhibitor (alpha 1-PI) occurred. This was caused by oxidation of a methionine residue at the active site of the alpha 1-PI, and offered indirect evidence of oxidation occurring in the inflamed pulmonary tissues. Studies with experimental animals have been initiated to gain understanding of the relative roles of proteases, oxidants, arachidonate metabolites, complement and contact system components, and other mediators in the pathogenesis of pulmonary inflammation. Intrabronchial instillation of glucose oxidase/glucose to produce oxidants or formylated norleucylleucylphenylalanine or phorbol myristate acetate as leukocytic stimuli induced severe acute pulmonary injury in New Zealand white rabbits and rhesus monkeys. The injury was accompanied by leukocytic protease (acid cathepsins) release in rabbit lungs and oxidant formation, and could be inhibited by neutrophil depletion. Oxidant formation was demonstrated by the inactivation of catalase by 3-amino-1,2,4-triazole in the presence of H2O2, a drop in intracellular glutathione levels, and in the rhesus monkey by inactivation of alpha 1-PI.
D000818:Animals; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007231:Infant, Newborn; D008264:Macrophages / Q000378:metabolism; D009504:Neutrophils / Q000201:enzymology; D010196:Pancreatic Elastase / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D011014:Pneumonia / Q000503:physiopathology*; D011650:Pulmonary Alveoli / Q000378:metabolism; D011654:Pulmonary Edema / Q000503:physiopathology; D011817:Rabbits; D012127:Respiratory Distress Syndrome, Newborn / Q000503:physiopathology*; D000515:alpha 1-Antitrypsin / Q000378:metabolism
D000515:alpha 1-Antitrypsin; D006861:Hydrogen Peroxide; D010447:Peptide Hydrolases; D010196:Pancreatic Elastase; D005978:Glutathione