title: Effects of induced mast cell activation on prostaglandin E and metalloproteinase production by rheumatoid synovial tissue in vitro.
abstract: 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.
  
  
  CONCLUSIONS
  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.affiliation: University Department of Medicine, Manchester Royal Infirmary.
authors.forename: L C
authors.initials: LC
authors.lastname: Tetlow
authors.forename: N
authors.initials: N
authors.lastname: Harper
authors.forename: T
authors.initials: T
authors.lastname: Dunningham
authors.forename: M A
authors.initials: MA
authors.lastname: Morris
authors.forename: H
authors.initials: H
authors.lastname: Bertfield
authors.forename: D E
authors.initials: DE
authors.lastname: Woolley
mesh_terms: D001172:Arthritis, Rheumatoid / Q000276:immunology*; D015153:Blotting, Western; D053818:Chymases; D017364:Collagenases / Q000032:analysis; D046508:Culture Techniques; D015232:Dinoprostone / Q000032:analysis / Q000096:biosynthesis*; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D004797:Enzyme-Linked Immunosorbent Assay; D018093:Gelatinases / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000032:analysis; D008407:Mast Cells / Q000201:enzymology / Q000378:metabolism*; D020781:Matrix Metalloproteinase 1; D020778:Matrix Metalloproteinase 2; D019278:Matrix Metalloproteinase 3 / Q000032:analysis; D008666:Metalloendopeptidases / Q000032:analysis / Q000096:biosynthesis*; D012697:Serine Endopeptidases / Q000032:analysis; D013583:Synovial Membrane / Q000276:immunology*; D053802:Tryptases
chemical_list: D018836:Inflammation Mediators; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; D053802:Tryptases; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1; D015232:Dinoprostone