Lung injury and repair in the blotchy mouse. Effects of nitrogen dioxide inhalation.
We studied the reparative process after inhalation exposure to 20 ppm of nitrogen dioxide (NO2) in the lungs of hemizygous blotchy male (Blo/g) and heterozygous blotchy female (Bio/+) mice. Age-matched siblings (C3Hf) without the blotchy gene at X-chromosome locus (+/y) and +/+) served as control animals. After exposure to NO2 for 28 days, there was a marked progression in the extent of emphysema in Blo/y mice associated with a significant decrease of internal surface area (p < 0.05) and an increase in the mean linear intercept (p < 0.005). In contrast, +/y, Blo/+, and +/+ mice showed mild airspace enlargement without decrease in internal surface area after similar exposures. Blo/y mice killed 1 month after cessation of NO2 exposure showed a persistent, mild chronic bronchiolitis that was more frequent and of greater severity than that present in control +/y mice. Alveolar macrophages in the Blo/y mice were larger than those in +/y, +/+, and Blo/+ mice both before and after exposure to NO2. Crystalloid inclusions were observed in the enlarged alveolar macrophages of the Blo/g mice only after exposure to NO2, but were not seen in control animals. These observations indicate that the pattern of lung injury and repair after subacute exposure to 20 ppm of NO2 in the Blo/y mouse differs from that present in age-matched siblings in that inherited abnormalities in alveolar macrophage function may exist in addition to the previously described alterations in connective tissue proteins. Both of these alterations may influence the development of emphysema in the blotchy male mouse.
D000818:Animals; D003095:Collagen Diseases / Q000235:genetics / Q000503:physiopathology; D005260:Female; D008168:Lung / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced*; D008176:Lung Volume Measurements; D008264:Macrophages / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains / Q000502:physiology*; D009585:Nitrogen Dioxide / Q000009:adverse effects*; D008249:Protein-Lysine 6-Oxidase / Q000172:deficiency; D011650:Pulmonary Alveoli / Q000166:cytology; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000473:pathology
D008249:Protein-Lysine 6-Oxidase; D009585:Nitrogen Dioxide