Hyperoxic lung injury in mice: effect of neutrophil depletion and food deprivation.
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.
Smith
L J
LJ
Department of Medicine, Northwestern University, Chicago, IL.
Friedman
H
H
Anderson
J
J
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
D011506:Proteins; D008466:Mechlorethamine; D010100:Oxygen