Leukocyte-mediated epithelial injury in ozone-exposed rat lung.
Both epithelial injury and inflammation are characteristic findings in the centriacinar regions of the lungs of rats exposed to ozone. In humans such effects could lead to long-term lung damage and disease. In animals, neoplastic change in the lungs after exposure to ozone has been described previously. The possible relationships between inflammatory cell recruitment, epithelial injury, and hyperplasia, with special regard to the important role of repair processes in leading to increased incidence of tumors in some species, have been addressed in the present study. We have previously described that leukocytes from lungs inflamed by different agents can injure epithelial cells in vitro. We have suggested that this leukocyte-mediated epithelial injury could enhance epithelial turnover in ozone-exposed lungs and so enhance the likelihood of tumor development. We, therefore, set out to test the hypothesis that bronchoalveolar leukocytes from ozone-exposed lungs can injure epithelial cells in vitro. PVG rats were exposed to 0.2, 0.4, 0.6, and 0.8 parts per million2 (ppm) ozone for seven hours per day for up to four days. On the morning following the last exposure, bronchoalveolar lavage was used to sample the bronchoalveolar leukocytes and the following parameters were assessed: total number, differential leukocyte count, production of oxidants, ability to degrade fibronectin, and ability to injure epithelial cells. In addition to these parameters, which were measured at all concentrations and time points in limited experiments, we also assessed macrophage size in short-term culture and inflammation in histological sections of lungs. Total number of lavageable cells was not affected by ozone inhalation. However, the percentage of macrophages decreased with ozone treatment and the percentage of neutrophils increased on days 1 and 2 at 0.6 and 0.8 ppm ozone. There was no significant effect of ozone exposure on the ability of neutrophils to degrade fibronectin or injure epithelial cells. Production of superoxide anion in response to stimulation with phorbol myristate acetate was significantly decreased by exposure to 0.6 ppm ozone, as described in previous studies. Macrophages from the lungs of rats exposed to ozone were larger than control macrophages.
Donaldson
K
K
Institute of Occupational Medicine, Edinburgh, Scotland.
Brown
G M
GM
Brown
D M
DM
Slight
J
J
Maclaren
W M
WM
Davis
J M
JM
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004847:Epithelial Cells; D004848:Epithelium / Q000293:injuries; D066298:In Vitro Techniques; D007249:Inflammation / Q000503:physiopathology; D007958:Leukocyte Count; D007962:Leukocytes / Q000378:metabolism*; D008168:Lung / Q000473:pathology; D055370:Lung Injury; D008175:Lung Neoplasms / Q000209:etiology* / Q000473:pathology; D008264:Macrophages / Q000502:physiology; D009504:Neutrophils / Q000502:physiology; D010126:Ozone / Q000009:adverse effects*; D051381:Rats
D010126:Ozone