An inhibitor of mammalian collagenase from foetal rabbit bone in culture.

There is ample evidence to indicate an important role for specific collagenases in the turnover of connectivetissue collagens both in normal and pathological conditions (Harris & Krane, 1974a,b,c). It has been the aim of many investigators to define the stimuli controlling the synthesis and secretion of collagenase, but it is clear that the extracellular control of the activity of collagenase is also important. Two mechanisms have been proposed for this control. In the first it is suggested that collagenase is released from cells or tissues as a proenzyme which is converted into active collagenase extracellularly by limited proteolytic cleavage (Vaes, 1972; Harper & Gross, 1972; Kruze & Wojtecka, 1972; Hook et al., 1973). The second mechanism proposes that active collagenase is released from cells and tissues and that the extent of its subsequent extracellular action is modified by inhibitors (Bauer et al., 1972,1975; Nagai, 1973; Woolley et al., 1976). The relative contribution of these two mechanisms to collagenase regulation in vivo is not yet clear. In this communication we report the production, by rabbit bone, of a low-molecular-weight inhibitor of collagenase and speculate on its role in the control of extracellular collagenase activity. Parietal bone explants from foetal rabbits (22-29 days of gestation) in culture synthesize a specific collagenase as characterized by its action on collagen in solution at 25°C and its sensitivity to inhibitors of the various classes of proteinases. The enzyme, which is a metalloproteinase, exists in both latent and active forms. We call the active enzyme native collagenase to distinguish it from activated collagenase produced by treatment of latent