Role of neutrophils and nitric oxide in lung alveolar injury from smoke inhalation.
We examined potential mechanisms responsible for the parenchymal lung injury seen in an animal model of smoke inhalation with concurrent inflammation. Rats injected with sterile glycogen and exposed to smoke generated by the nonflaming pyrolysis of combined Douglas fir wood and polyvinylchloride showed a 74% increase in 125I-albumin lung permeability and a fivefold increase in lung myeloperoxidase (MPO) compared with control rats. There was also a significant increase in plasma indices of oxidative injury in these animals. Compared with control animals, plasma concentrations of thiobarbituric acid reactive substances (TBARS) were elevated by 62%, the concentrations of reduced sulfhydryl groups declined by 37%, and the levels of dinitrophenylhydrazine-reactive proteins (DNPH-RP) were doubled. In addition, the plasma concentrations of nitrate (NO3-) in rats exposed to glycogen plus smoke were increased three times that of control animals. Injection of the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), immediately after smoke exposure or induction of neutropenia using either nitrogen mustard or antineutrophil antiserum, abolished the increase in concentrations of circulating NO3-, and prevented changes in plasma concentrations of TBARS, DNPH-RP, lung MPO activity, and tissue permeability index. These data suggest that neutrophil activation and the production of nitric oxide-derived oxidants contribute to the lung and plasma indices of oxidative injury in this smoke inhalation model.
Ischiropoulos
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Institute for Environmental Medicine, University of Pennsylvania, School of Medicine, Philadelphia 19104-6068.
Mendiguren
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Fisher
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Fisher
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Thom
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D019297:2,4-Dinitrophenol; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004140:Dinitrophenols / Q000097:blood; D006003:Glycogen / Q000494:pharmacology; D015227:Lipid Peroxidation; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009504:Neutrophils / Q000502:physiology*; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D010539:Permeability; D009195:Peroxidase / Q000032:analysis; D011650:Pulmonary Alveoli / Q000201:enzymology / Q000503:physiopathology*; D051381:Rats; D011916:Rats, Inbred F344; D015208:Smoke Inhalation Injury / Q000378:metabolism / Q000503:physiopathology*; D013438:Sulfhydryl Compounds / Q000097:blood; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
D004140:Dinitrophenols; D009566:Nitrates; D013438:Sulfhydryl Compounds; D017392:Thiobarbituric Acid Reactive Substances; D009569:Nitric Oxide; D006003:Glycogen; D001120:Arginine; D009195:Peroxidase; D019297:2,4-Dinitrophenol; D019331:NG-Nitroarginine Methyl Ester