Genetic susceptibility to irritant-induced acute lung injury in mice.
Recent studies suggest that genetic variability can influence irritant-induced lung injury and inflammation. To begin identifying genes controlling susceptibility to inhaled irritants, seven inbred mouse strains were continuously exposed to nickel sulfate (NiSO(4)), polytetrafluoroethylene, or ozone (O(3)), and survival time was recorded. The A/J (A) mouse strain was sensitive, the C3H/He (C3) strain was intermediate, and the C57BL/6 (B6) strain was resistant to NiSO(4)-induced acute lung injury. The B6AF(1) offspring were also resistant. The strain sensitivity pattern for NiSO(4) exposure was similar to that of polytetrafluoroethylene or ozone (O(3)). Pulmonary pathology was comparable for A and B6 mice. In the A strain, 15 microg/m(3) of NiSO(4) produced 20% mortality. The strain sensitivity patterns for lavage fluid proteins (B6 > C3 > A) and neutrophils (A >/= B6 > C3) differed from those for acute lung injury. This phenotype discordance suggests that these traits are not causally linked (i.e., controlled by independent arrays of genes). As in acute lung injury, B6C3F(1) offspring exhibited phenotypes (lavage fluid proteins and neutrophils) resembling those of the resistant parental strain. Agreement of acute lung injury strain sensitivity patterns among irritants suggested a common mechanism, possibly oxidative stress, and offspring resistance suggested that sensitivity is inherited as a recessive trait.
Wesselkamper
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SC
Departments of Environmental Health, Molecular and Cellular Physiology, Medicine, and Civil and Environmental Engineering, University of Cincinnati, Cincinnati, Ohio 45267, USA.
Prows
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Biswas
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Willeke
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Bingham
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Leikauf
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GD
D000208:Acute Disease; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D005799:Genes, Dominant; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease / Q000235:genetics; D007509:Irritants; D007962:Leukocytes / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced* / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains; D009532:Nickel / Q000494:pharmacology; D010641:Phenotype; D011506:Proteins / Q000032:analysis
D007509:Irritants; D011506:Proteins; C029938:nickel sulfate; D009532:Nickel