title: Ovalbumin-induced airway inflammation and fibrosis in mice also exposed to ozone.
abstract: A murine model of allergen-induced airway inflammation was used to examine the effects of exposure to ozone on airway inflammation and remodeling. Sensitized BALB/c mice were exposed to ovalbumin aerosol for 4 wk before and after 2 wk of exposure to either 0.2 ppm or 0.5 ppm ozone. Other groups of mice were exposed to ovalbumin aerosol for 6 wk with continuous concurrent exposure to ozone during wk 1-6, or during intermittent concurrent exposure to ozone. Lung inflammation was measured by quantitative differential evaluation of lung lavage cells and by histological evaluation of stained lung sections. Alterations in lung structure (airway fibrosis) were evaluated by quantitative biochemical analysis of microdissected airways. The same total number of cells was observed in lavage fluid from animals exposed for 4 wk to ovalbumin alone or to ovalbumin for 4 wk immediately before or after exposure to 2 wk of 0.2 or 0.5 ppm ozone. Mice exposed to ovalbumin for 6 wk with concurrent exposure to either 0.2 ppm or 0.5 ppm ozone during wk 3-6 had a significant decrease in the total number of cells recovered by lavage. Values as low as 7% of the cell number found in mice exposed to ovalbumin aerosol alone were observed in the mice exposed to ovalbumin plus 0.2 ppm ozone during wk 3-6. There were significant differences in the cell differential counts in the lavage fluid from mice exposed to ovalbumin alone as compared with values from mice exposed to ovalbumin and ozone under all of the protocols studied. When ozone was given for 2 wk prior to ovalbumin exposure (Experiment 1), there were a high percentage of macrophages and low percentages of lymphocytes and eosinophils in the lung lavage. When ozone was given for 2 wk after ovalbumin exposure (Experiment 2), there were a moderate percentage of macrophages, a low percentage of eosinophils, and a high percentage of lymphocytes in the lung lavage. When ozone and ovalbumin were given simultaneously (Experiments 3 and 4), there were a high percentage of macrophages in the lavage with 0.2 ppm ozone and a high percentage of eosinophils. Ozone appears to antagonize the specific inflammatory effects of ovalbumin exposure, especially when given before or during exposure to ovalbumin. Airway remodeling was examined by two different quantitative methods. None of the groups exposed concurrently to ovalbumin and ozone had a significant increase in airway collagen content as compared to the matched groups of mice exposed to ovalbumin alone. The findings were consistent with an additive response of mice to simultaneous exposure to ovalbumin and ozone. Ozone exposure alone for 6 wk did not affect the number of goblet cells in the airways, while mice exposed to ovalbumin aerosol alone for 6 wk had about 25% goblet cells in their conducting airways. Concurrent exposure to ovalbumin and 0.2 ppm ozone caused significant increases in goblet cells (to 43% of total cells) in the conducting airways of the exposed mice. We conclude that when mice with allergen-induced airway inflammation induced by ovalbumin are also exposed to ozone, the lung inflammatory response may be modified, but that this altered response is dependent on the sequence of exposure and the concentration of ozone to which they are exposed. At the concentrations of ozone tested, we did not see changes in airway fibrosis. However, goblet-cell hyperplasia appeared to be increased in mice exposed concurrently to ovalbumin and 0.2 ppm ozone.
authors.affiliation: Pulmonary and Critical Care Medicine, School of Medicine, University of California, Davis, California 95616-8723, USA. jalast@ucdavis.edu
authors.forename: Jerold A
authors.initials: JA
authors.lastname: Last
authors.forename: Rachel
authors.initials: R
authors.lastname: Ward
authors.forename: Lisa
authors.initials: L
authors.lastname: Temple
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Kenyon
mesh_terms: D000336:Aerosols; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D004396:Coloring Agents; D005355:Fibrosis; D006909:Hydroxyproline / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology*; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000633:toxicity*; D010126:Ozone / Q000633:toxicity*; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D012140:Respiratory Tract Diseases / Q000139:chemically induced / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016707:Tissue Fixation
chemical_list: D000336:Aerosols; D004396:Coloring Agents; D011506:Proteins; D010126:Ozone; D010047:Ovalbumin; D006909:Hydroxyproline