Changes in collagen metabolism and proteinolysis after repeated inhalation exposure to ozone.

To study the changes in collagen metabolism that occur in the pathogenesis of pulmonary fibrosis, female rats were exposed to 0, 0.57, and 1.1 ppm ozone for 19 hr/day for 11 days and sacrificed 12 or 60 days after initiation of exposure. The lungs of rats sacrificed at 12 days after initiation of exposure to 1.1 ppm had interstitial pneumonia characterized by a mixed inflammatory cell infiltrate, type II cell hyperplasia, and fibroplasia, a proliferation of the collagen-producing cells; increased cathepsin D and macrophage elastase activity, indicating macrophage-induced proteinolysis; a reduced percentage of the increased collagen production that was ultrafilterable, indicating a decreased rate of intracellular degradation of newly produced collagen prior to its secretion; and increased lavage fluid hydroxyproline, indicating turnover of extracellular collagenous matrix. Reduced intracellular collagen degradation correlated directly with both increased net collagen production and fibroplasia in rats exposed to 1.1 ppm ozone for 11 days. These changes preceded an increased total lung collagen and the development of modest fibroplasia and fibrosis in the alveolar duct regions by 60 days after the 1.1 ppm ozone exposure was initiated.