This laboratory is interested principally in the rheumatoid synovial membrane and the degradative enzymes that it releases which have the capability of destroying cartilage, tendon and bone. Having started with organ cultures of synovial tissue we have moved since to cultures of dissociated synovial cells. In the past year we have characterized the manner in which latent collagenase is released from cells, binds to substrate and subsequently is activated by at least one proteinase present in vivo, plasmin. We plan to study whether latent collagenase is released as a zymogen or as an enzyme-inhibitor complex. We plan to utilize a system of culturing rheumatoid synovial cells on a collagen film in vitro to trap latent collagenase from cells and bound to fibrils. We can utilize this system to evaluate suppressive effects of drugs on collagenase synthesis and release by cells. BIBLIOGRAPHIC REFENCES: Harris, E.D., Jr.: Treatment of scleroderma, in Current Therapy (H.F. Conn, editor). Philadelphia: W.B. Saunders Co., 1977, pp. 691-695. Harris, E.D., Jr., Clauert, A.M., and Murley, A.H.G.: Intracellular collagen fibers at the pannus/cartilage junction in rheumatoid arthritis. Arthritis Rheum. 20: 657-665, 1977.