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Bleomycin-induced Increase of Collagen Turnover in IMR-90 Fibroblasts: An in Vitro Model of Connective Tissue Restructuring during Lung Fibrosis¹

Department of Biochemistry, College of Medicine, University of Vermont, Burlington, Vermont 05405

Late-log-phase IMR-90 human fetal lung fibroblasts were incubated with bleomycin sulfate for 48 hr. The culture medium was removed and replaced with serum-free medium and [5-³H]proline. The cells were then incubated for increasing time intervals. The cells and culture medium were collected, and radioactive proline incorporated into collagen and noncollagen protein was determined. Intracellular collagen synthesis was selectively increased. Furthermore, polysomes isolated from bleomycin-treated cells synthesized significantly more collagen in the wheat germ lysate than did control polysomes. Prolyl hydroxylase activity was also increased significantly in the bleomycin-treated cells. Free and peptide-bound radioactive hydroxyproline in the cells and medium was greatly increased in bleomycin-treated cells, which indicates increased collagen degradation. The results demonstrate that, although collagen synthesis in lung fibroblasts is increased by bleomycin, the newly synthesized collagen is rapidly degraded in both the cell layer and the medium. This increased collagen degradation may be responsible for the remodeling which takes place during lung fibrosis.

¹ Supported by NIH Grants HL 23607, HL 14212, and AM 19808.

² To whom requests for reprints should be addressed.

Received 12/10/81. Accepted 6/ 7/82.