title: Hyperoxic lung injury in mice: effect of neutrophil depletion and food deprivation.
abstract: Conflicting data exist on the role of neutrophils (PMNs) in the pathogenesis of hyperoxic lung damage. We examined the contribution of PMNs and the contribution of food deprivation, a frequent complication of the methods used to produced neutropenia, to the lung damage that results when mice are exposed to high concentrations of oxygen. Mice were exposed to either 100% oxygen or air for up to 4 days. Neutropenia was induced by a single tail vein injection of nitrogen mustard (NM) given 1 day before the oxygen exposure. Food deprivation, which induced the same weight loss as that found in NM-treated mice, was achieved by withholding food (fasted) during the oxygen exposure. We examined mortality; weight loss; bronchoalveolar lavage (BAL fluid) protein concentration, cell count, and differential count; the number of PMNs in blood; and lung histologic conditions by light and electron microscopy. NM-treated mice lost approximately 25% of their body weight when exposed to either air or oxygen. They also had more severe lung damage than the saline-treated mice during hyperoxic exposure, despite a marked reduction in the number of PMNs in blood, BAL fluid, and lung tissue. Although a correlation was found between the number of blood PMNs and the BAL protein concentration in the nonneutropenic mice (r = 0.69; P less than 0.001), no correlation was seen in the neutropenic mice (r = 0.26). Fasted, oxygen-exposed mice had the same weight loss as the NM mice, but they had more severe lung damage at an earlier time (day 3 vs. day 4) and greater mortality than the saline-treated and the NM-treated mice. These results indicate that PMNs are not required for either the development or progression of hyperoxic lung damage in mice; fasting increases susceptibility to the lung damage; and differences in nutritional status may explain, in part, the controversial role of PMNs in oxygen-induced lung damage.
authors.affiliation: Department of Medicine, Northwestern University, Chicago, IL.
authors.forename: L J
authors.initials: LJ
authors.lastname: Smith
authors.forename: H
authors.initials: H
authors.lastname: Friedman
authors.forename: J
authors.initials: J
authors.lastname: Anderson
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000378:metabolism / Q000473:pathology; D005508:Food Deprivation / Q000502:physiology*; D008168:Lung / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008466:Mechlorethamine / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009503:Neutropenia / Q000473:pathology; D009504:Neutrophils / Q000502:physiology*; D010100:Oxygen / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism
chemical_list: D011506:Proteins; D008466:Mechlorethamine; D010100:Oxygen