Proteases induce secretion of collagenase and plasminogen activator by fibroblasts.
We have observed that treatment of rabbit synovial fibroblasts with proteolytic enzymes can induce secretion of collagenase (EC 3.4.24.7) and plasminogen activator (EC 3.4.21.-). Cells treated for 2-24 hr 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 hr. Treatment of fibroblasts with trypsin also induced secretion of plasminogen activator. Proteases initiated secretion of collagenase (up to 20 units per 10(6) cells per 24 hr) 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 have not been identified. These results suggest that extracellular proteases in conjunction with plasma proteins may govern protease secretion by cells.
D001798:Blood Proteins / Q000494:pharmacology; D002478:Cells, Cultured; D003470:Culture Media; D005341:Fibrinolysin / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D003012:Microbial Collagenase / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism*; D010960:Plasminogen Activators / Q000378:metabolism*; D014357:Trypsin / Q000378:metabolism
D001798:Blood Proteins; D003470:Culture Media; D010447:Peptide Hydrolases; D010960:Plasminogen Activators; D014357:Trypsin; D005341:Fibrinolysin; D003012:Microbial Collagenase