The control of fibrogenesis: stimulation and suppression of collagen synthesis in the chick chorioallantoic membrane with fibrin degradation products, wound extracts and proteases.

The chick chorioallantoic membrane model (CAM) has previously been used to demonstrate cell proliferation, characteristic of both angiogenesis and fibrogenesis, after exposure to fibrin degradation products. This model has now been adapted for quantitative in vivo assay of collagen polypeptide synthesis and prolyl hydroxylase activity. The CAM exhibits oscillations in the level of labelled collagen, a pattern attributable to rapid intracellular degradation and proline recycling following a brief labelling period. Both collagen synthesis and prolyl hydroxylase activity are stimulated by fibrin degradation products (less than 50 000 MW). Such stimulation occurs by 3 h and precedes the rise in general protein synthesis. Extracts of healing mouse skin wounds, rich in proteases, inhibited collagen synthesis, as did pure plasmin. Conversely, stimulation was achieved when proteolytic activity was neutralized by soybean trypsin inhibitor. These findings help to explain the observation that fibroblasts and endothelial cells proliferate and migrate centrally in an inflammatory lesion without depositing collagen, whilst in a milieu of high proteolytic activity. More peripherally, where proteases are inactivated by antiproteases in inflammatory exudate, such cell movement ceases and collagen deposition is observed.