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Title: Proteases induce secretion of collagenase and plasminogen activator by fibroblasts

Abstract

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 to 24 hr with plasmin, trypsin, chymotrypsin, pancreatic elastase, papain, bromelain, thermolysin, or ..cap alpha..-protease but not with thrombin or neuraminidase secreted detectable amounts of collagenase within 16 to 48 hr. Treatment of fibroblasts with trypsin also induced secretion of plasminogen activator. Proteases initiated secretion of collagenase (up to 20 units per 10/sup 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, ..cap alpha../sub 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 havemore » not been identified. These results suggest that extracellular proteases in conjunction with plasma proteins may govern protease secretion by cells.« less

Authors:
;
Publication Date:
Research Org.:
Univ. of California, San Francisco
OSTI Identifier:
6851004
Alternate Identifier(s):
OSTI ID: 6851004
Resource Type:
Journal Article
Resource Relation:
Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States); Journal Volume: 75:4
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; ENZYME INHIBITORS; BLOOD SERUM; FIBROBLASTS; PEPTIDE HYDROLASES; SECRETION; BONE JOINTS; CELL CULTURES; RABBITS; ANIMAL CELLS; ANIMALS; BODY; CONNECTIVE TISSUE CELLS; ENZYMES; HYDROLASES; MAMMALS; ORGANS; SKELETON; SOMATIC CELLS; VERTEBRATES 550200* -- Biochemistry; 550300 -- Cytology

Citation Formats

Werb, Z., and Aggeler, J.. Proteases induce secretion of collagenase and plasminogen activator by fibroblasts. United States: N. p., 1978. Web. doi:10.1073/pnas.75.4.1839.
Werb, Z., & Aggeler, J.. Proteases induce secretion of collagenase and plasminogen activator by fibroblasts. United States. doi:10.1073/pnas.75.4.1839.
Werb, Z., and Aggeler, J.. Sat . "Proteases induce secretion of collagenase and plasminogen activator by fibroblasts". United States. doi:10.1073/pnas.75.4.1839.
@article{osti_6851004,
title = {Proteases induce secretion of collagenase and plasminogen activator by fibroblasts},
author = {Werb, Z. and Aggeler, J.},
abstractNote = {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 to 24 hr with plasmin, trypsin, chymotrypsin, pancreatic elastase, papain, bromelain, thermolysin, or ..cap alpha..-protease but not with thrombin or neuraminidase secreted detectable amounts of collagenase within 16 to 48 hr. Treatment of fibroblasts with trypsin also induced secretion of plasminogen activator. Proteases initiated secretion of collagenase (up to 20 units per 10/sup 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, ..cap alpha../sub 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.},
doi = {10.1073/pnas.75.4.1839},
journal = {Proc. Natl. Acad. Sci. U.S.A.; (United States)},
number = ,
volume = 75:4,
place = {United States},
year = {Sat Apr 01 00:00:00 EST 1978},
month = {Sat Apr 01 00:00:00 EST 1978}
}