Effects of induced mast cell activation on prostaglandin E and metalloproteinase production by rheumatoid synovial tissue in vitro

doi:10.1136/ard.57.1.25

Annals of the Rheumatic Diseases 1998;57:25-32; doi:10.1136/ard.57.1.25

Ann Rheum Dis 1998;57:25-32 ( January )

Extended reports

Effects of induced mast cell activation on prostaglandin E and metalloproteinase production by rheumatoid synovial tissue in vitro L C Tetlow,^a N Harper,^a T Dunningham,^b M A Morris,^c H Bertfield,^d D E Woolley^a

^a University Department of Medicine, Manchester Royal Infirmary, Manchester, ^b Tameside General Hospital, Manchester, ^c Devonshire Royal Hospital, Buxton, Derbyshire, ^d Wythenshawe Hospital, Manchester

Correspondence to: Dr D E Woolley, University Department of Medicine, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL.

Accepted for publication 22 October 1997

OBJECTIVE $---$ To determine whether induced mast cell activation/degranulation in rheumatoid synovial explants modulates the production ofprostaglandin E (PGE₂), and the matrix metalloproteinases (MMPs)collagenase 1, gelatinase A, and stromelysin1.
METHODS $---$ Synovial explant cultures were treated either with rabbit IgG anti-human IgE as a mast cell (MC) secretagogue or with non-immunerabbit IgG as controls. After 20 hours conditioned medium wasassayed for the release of MC tryptase, PGE₂, collagenase 1, gelatinaseA, and stromelysin 1 using radioimmunoassay, enzyme linked immunosorbentassay, western blot, and zymogram techniques; tissue explantswere examined immunohistologically for the relative distributionsof MC tryptase, collagenase 1, and stromelysin1.
RESULTS $---$ Over a 20 hour incubation period the MC secretagogue treated explants showed a significant increase in the quantities of releasedtryptase and PGE₂ compared with controls. By contrast, the threeMMPs showed variable values between experiments in response toMC activation; no reproducible trend of either an increased ordecreased production of each MMP over control values was evident.Each MMP initially appeared as an inactive precursor form; collagenase1 and stromelysin 1 were more effectively processed to activeforms in the MC activated cultures. Immunolocalisation studiesof MC activated explants showed that areas of extracellular tryptasewere commonly associated with the local production of both collagenase1 and stromelysin1.
CONCLUSION $---$ MC degranulation induced artificially in rheumatoid synovial explant cultures consistently resulted in an increased productionof PGE₂ but had variable effects on the quantification of releasedcollagenase 1, gelatinase A, and stromelysin 1. Such observationssupport the concept that activated synovial MCs within their nativeenvironment stimulate the production of non-MC derived PGE₂ andmay contribute to the regulation and processing of specific MMPs;both aspects represent important components of the inflammatoryand degradative processes of the rheumatoidlesion.

Keywords: mast cells; matrix metalloproteinases; prostaglandin E₂; rheumatoid synovium

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