Proteases induce secretion of collagenase and plasminogen activator by fibroblasts

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Abstract
Treatment of rabbit synovial fibroblasts with proteolytic enzymes induces secretion of collagenase (EC 3.4.24.7) and plasminogen activator (EC 3.4.21.-). Cells treated for 2-24 h with plasmin, trypsin, chymotrypsin, pancreatic elastase, papain, bromelain, thermolysin or .alpha.-protease but not with thrombin or neuraminidase secreted detectable amounts of collagenase within 16-48 h. Treatment of fibroblasts with trypsin also induced secretion of plasminogen activator. Proteases initiated secretion of collagenase (up to 20 units/106 cells per 24 h) only when treatment produced decreased cell adhesion. Collagenase production did not depend on continued presence of proteolytic activity or on subsequent cell adhesion, spreading or proliferation. Routine subculturing with crude trypsin also induced collagenase secretion by cells. Secretion of collagenase was prevented and normal spreading was obtained if the trypsinized cells were placed into medium containing fetal calf serum. Soybean trypsin inhibitor, .alpha.1-antitrypsin, bovine serum albumin, collagen and fibronectin did not inhibit collagenase production. Although proteases that induced collagenase secretion also removed surface glycoprotein, the kinetics of induction of cell protease secretion were different from those for removal of fibronectin. Physiological inducers of secretion of collagenase and plasminogen activator by cells were not identified. Extracellular proteases in conjunction with plasma proteins may govern protease secretion by cells.