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PMID: 2553780 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Synovial procollagenase activation by human mast cell tryptase dependence upon matrix metalloproteinase 3 activation.

The Journal of clinical investigation ·Vol. 84 ·No. 5 ·1989-11-00 ·Pages 1657-62

Gruber BL, Marchese MJ, Suzuki K, Schwartz LB, Okada Y, Nagase H, Ramamurthy NS

Abstract

Mast cells have been implicated in the pathogenesis of the matrix degradation observed in the cartilaginous and osseous structures of the rheumatoid joint. We previously reported that human mast cell tryptase, a 134-kD granule-associated neutral protease, is present in rheumatoid synovium and can activate collagenase in crude culture medium in vitro. the present study attempts to depict the precise mechanism of this activation. To express full activation of latent collagenase, matrix metalloproteinase 3 (MMP-3) or stromelysin, can be activated by tryptase in a time and dose-dependent manner. Tryptase was not capable of generating active collagenase in the crude media from cultured rheumatoid synoviocytes depleted of proMMP-3 by immunoadsorption. In addition, the function of the tissue inhibitor of metalloproteinases (TIMP) was not altered by tryptase, and SDS-PAGE analysis revealed no degradation of TIMP by tryptase. The tryptase dependent activation of synoviocyte procollagenase thereby appears to be entirely dependent upon its ability to activate proMMP-3.

MeSH Terms
Blotting, Western Collagen/metabolism Collagenases Enzyme Activation/drug effects Enzyme Precursors/metabolism Glycoproteins/pharmacology Humans Mast Cells/enzymology Matrix Metalloproteinase 3 Metalloendopeptidases/metabolism Microbial Collagenase/metabolism Peptide Hydrolases/pharmacology Synovial Membrane/enzymology Tissue Inhibitor of Metalloproteinases
Chemicals
Enzyme Precursors Glycoproteins Tissue Inhibitor of Metalloproteinases Collagen Peptide Hydrolases tosylarginine methyl ester hydrolase Collagenases Metalloendopeptidases procollagenase Matrix Metalloproteinase 3 Microbial Collagenase
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Gruber B L
Division of Allergy, Rheumatology and Clinical Immunology, Veterans Administration, Northport, New York 11768.
Marchese M J
Suzuki K
Schwartz L B
Okada Y
Nagase H
Ramamurthy N S
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI114344
Published
1989-11-00
Pages
1657-62
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC304033
Subset
IM
Grants
NIAID NIH HHS · AI-20487 · United States
NIAMS NIH HHS · AR-39189 · United States
NIDCR NIH HHS · DEO3987 · United States
External Links
PubMed source DOI: 10.1172/JCI114344 PMC Full Text View journal details
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