Protein metabolism during bleomycin-induced pulmonary fibrosis in rabbits. In vivo evidence for collagen accumulation because of increased synthesis and decreased degradation of the newly synthesized collagen.

Abstract

In vivo rates of synthesis and degradation of collagen and noncollagen protein were measured in normal lung and during the first 14 days of bleomycin-induced pulmonary fibrosis in rabbits. Protein synthesis rates were obtained by measuring the incorporation of labeled proline into tissue proteins after the injection of 3H-proline with a large amount of unlabeled proline. Degradation rates were assessed by several independent methods, including measurement of hydroxy-3H-proline in the tissue-free pool as an index of the degradation of newly synthesized collagen. In normal lung, collagen was synthesized and degraded at a rate of 9.5 +/- 1.5%/day compared with a rate of 34.6 +/- 1.9%/day for noncollagen proteins. About one third of the newly synthesized collagen was degraded rapidly after its production. Six days after bleomycin administration the collagen synthesis rate almost doubled and the synthesis rate of noncollagen protein increased by about 35%. At this time the degradation rate of newly synthesized collagen had decreased by about 30%. From this study we conclude: (1) that the lung is an active tissue in terms of protein metabolism with rapid turnover for both collagen and noncollagen proteins, and (2) that an increased rate of synthesis and a decreased rate of degradation contribute to rapid accumulation of collagen in the early stages of pulmonary fibrosis.