COLLAGEN BREAKDOWN PRODUCTS AND LUNG COLLAGEN-METABOLISM - AN IN-VITRO STUDY ON FIBROBLAST-CULTURES

Background - In fibrotic diseases such as pulmonary fibrosis there is evidence suggesting enhanced synthesis and degradation of lung connect ive tissue components, including collagen. It has therefore been hypot hesised that products of collagen degradation may have a role in the p romotion of collagen deposition. In support of this hypothesis, it has recently been shown that intravenous injection of lung collagen degra dation products in experimental animals stimulated collagen synthesis leading to increased collagen deposition and diffuse interstitial lung disease. Methods - Rabbit and human fibroblast cultures from lung and skin were used as an in vitro model to study the responses of these c ells to rabbit collagen degradation products. The effects of an acute exposure to collagen degradation products on synthesis of collagen and noncollagenous protein have been studied in confluent cultures by H- 3-proline incorporation. The effects of collagen degradation products on fibroblast proliferation and production of genetic types of collag en have also been investigated. Results - The acute exposure of rabbit lung fibroblast cultures to collagen degradation products significant ly increased collagen synthesis without affecting non-collagenous prot ein synthesis. This effect was dose related, specific for lung fibrobl asts, and species specific. Collagen degradation products altered the rate of synthesis of genetic types of collagen with a consequent decre ase of type III/I+III collagen ratio (0.26 (0.04) treated with collage n degradation products; 0.45 (0.02) controls). These effects occurred without the intervention of serum factors. In addition, collagen degra dation products neither affected fibroblast proliferation nor selected specific clones emphasising one type of collagen. Conclusions - These results suggest that collagen degradation products can influence lung collagen metabolism by stimulating collagen synthesis. The regulation of collagen mass by collagen degradation products may be of importanc e in lung collagen homeostasis in vivo.