PULMONARY FIBROSIS IN EXPERIMENTAL ACUTE RESPIRATORY-DISEASE

Abstract

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 (i.p.), ozone (inhaled) or bleomycin (intratracheally injected). After an interval sufficient to allow histologically discernible fibrosis to occur (6-7 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 (several-fold) in the apparent collagen synthesis rates by lung minces from all the pneumotoxin-exposed rats. 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, type I/type III collagen was quantified for newly synthesized, 3H-labeled collagen, and for total unlabeled collagen. In lung minces from normal rats the ratio was 2:1 (65-70% type I collagen) for both newly synthesized and total collagen. Lung minces prepared from fibrotic rats accumulated a mixture of newly synthesized collagens that were substantially enriched for type I collagen (80-85% 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. An early event in experimental acute respiratory disease is a marked increase in the relative synthesis of type I collagen; this shift occcurs before there is observable increased accumulation of collagen in the lung.