Document Detail


Effects of induced mast cell activation on prostaglandin E and metalloproteinase production by rheumatoid synovial tissue in vitro.
MedLine Citation:
PMID:  9536819     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To determine whether induced mast cell activation/degranulation in rheumatoid synovial explants modulates the production of prostaglandin E (PGE2), and the matrix metalloproteinases (MMPs) collagenase 1, gelatinase A, and stromelysin 1. METHODS: Synovial explant cultures were treated either with rabbit IgG anti-human IgE as a mast cell (MC) secretagogue or with non-immune rabbit IgG as controls. After 20 hours conditioned medium was assayed for the release of MC tryptase, PGE2, collagenase 1, gelatinase A, and stromelysin 1 using radioimmunoassay, enzyme linked immunosorbent assay, western blot, and zymogram techniques; tissue explants were examined immunohistologically for the relative distributions of MC tryptase, collagenase 1, and stromelysin 1. RESULTS: Over a 20 hour incubation period the MC secretagogue treated explants showed a significant increase in the quantities of released tryptase and PGE2 compared with controls. By contrast, the three MMPs showed variable values between experiments in response to MC activation; no reproducible trend of either an increased or decreased production of each MMP over control values was evident. Each MMP initially appeared as an inactive precursor form; collagenase 1 and stromelysin 1 were more effectively processed to active forms in the MC activated cultures. Immunolocalisation studies of MC activated explants showed that areas of extracellular tryptase were commonly associated with the local production of both collagenase 1 and stromelysin 1. CONCLUSION: MC degranulation induced artificially in rheumatoid synovial explant cultures consistently resulted in an increased production of PGE2 but had variable effects on the quantification of released collagenase 1, gelatinase A, and stromelysin 1. Such observations support the concept that activated synovial MCs within their native environment stimulate the production of non-MC derived PGE2 and may contribute to the regulation and processing of specific MMPs; both aspects represent important components of the inflammatory and degradative processes of the rheumatoid lesion.
Authors:
L C Tetlow; N Harper; T Dunningham; M A Morris; H Bertfield; D E Woolley
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Annals of the rheumatic diseases     Volume:  57     ISSN:  0003-4967     ISO Abbreviation:  Ann. Rheum. Dis.     Publication Date:  1998 Jan 
Date Detail:
Created Date:  1998-04-16     Completed Date:  1998-04-16     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0372355     Medline TA:  Ann Rheum Dis     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  25-32     Citation Subset:  IM    
Affiliation:
University Department of Medicine, Manchester Royal Infirmary.
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MeSH Terms
Descriptor/Qualifier:
Arthritis, Rheumatoid / immunology*
Blotting, Western
Chymases
Collagenases / analysis
Culture Techniques
Dinoprostone / analysis,  biosynthesis*
Electrophoresis, Polyacrylamide Gel
Enzyme Activation
Enzyme-Linked Immunosorbent Assay
Gelatinases / analysis
Humans
Immunohistochemistry
Inflammation Mediators / analysis
Mast Cells / enzymology,  metabolism*
Matrix Metalloproteinase 1
Matrix Metalloproteinase 2
Matrix Metalloproteinase 3 / analysis
Metalloendopeptidases / analysis,  biosynthesis*
Serine Endopeptidases / analysis
Synovial Membrane / immunology*
Tryptases
Chemical
Reg. No./Substance:
0/Inflammation Mediators; 363-24-6/Dinoprostone; EC 3.4.21.-/Serine Endopeptidases; EC 3.4.21.-/chymase 2; EC 3.4.21.39/Chymases; EC 3.4.21.59/Tryptases; EC 3.4.24.-/Collagenases; EC 3.4.24.-/Gelatinases; EC 3.4.24.-/Metalloendopeptidases; EC 3.4.24.17/Matrix Metalloproteinase 3; EC 3.4.24.24/Matrix Metalloproteinase 2; EC 3.4.24.7/Matrix Metalloproteinase 1
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