Pulmonary fibrosis in experimental acute respiratory disease.
Changes in collagen metabolism were examined in 3 models of acute respiratory disease in rats. Fibrotic changes in the lungs of rats were provoked by exposing them to paraquat (intraperitoneal), ozone (inhaled), or bleomycin (intratracheally injected). After an interval sufficient to allow histologically discernible fibrosis to occur (6 to 7 days), lungs were removed from the rats, and apparent collagen synthesis rates were determined with cultured lung minces incubated in medium containing 3H-proline. There was a significant increase (severalfold in the apparent collagen synthesis rates by lung minces from all the pneumotoxin-exposed rats in this study. Portions of the 3H-proline-labeled lung minces were then used for quantifying ratios of Type I to Type III collagen. Using CNBr mapping techniques and a combination of carboxymethylcellulose chromatography and polyacrylamide gel electrophoresis, we quantified Type I/Type III collagen for newly synthesized, 3H-labeled collagen as well as for total unlabeled collagen. In lung minces from normal rats, the ratio was 2:1 (65 to 70% Type I collagen) for both newly synthesized and total collagen. On the other hand, lung minces prepared from fibrotic rats accumulated a mixture of newly synthesized collagens that was substantially enriched for Type I collagen (80 to 85% Type I). There was no change in Type I/Type III collagen for total unlabeled collagen, nor was there any detectable increase of total collagen per lung after 1 wk. We conclude that an early event in experimental acute respiratory disease is a marked increase in the relative synthesis of Type I collagen; this shift occurs before there is observable increased accumulation of collagen in the lung.
D000208:Acute Disease; D000818:Animals; D001761:Bleomycin; D003094:Collagen / Q000096:biosynthesis*; D004195:Disease Models, Animal; D008171:Lung Diseases / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D010126:Ozone; D010269:Paraquat; D011658:Pulmonary Fibrosis / Q000378:metabolism*; D051381:Rats; D012128:Respiratory Distress Syndrome / Q000378:metabolism
D001761:Bleomycin; D010126:Ozone; D003094:Collagen; D010269:Paraquat