EFFECTS OF INDUCED MAST-CELL ACTIVATION ON PROSTAGLANDIN-E AND METALLOPROTEINASE PRODUCTION BY RHEUMATOID SYNOVIAL TISSUE IN-VITRO

Objective-To determine whether induced mast cell activation/degranulat ion in rheumatoid synovial explants modulates the production of prosta glandin E (PGE,), 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 hou rs conditioned medium was assayed for the release of MC tryptase, PGE, , collagenase 1, gelatinase A, and stromelysin 1 using radioimmunoassa y, enzyme linked immunosorbent assay, western blot, and zymogram techn iques; tissue explants were examined immunohistologically for the rela tive distributions of MC tryptase, collagenase 1, and stromelysin 1. R esults-Over a 20 hour incubation period the MC secretagogue treated ex plants showed a significant increase in the quantities of released try ptase and PGE, compared with controls. By contrast, the three MMPs sho wed variable values between experiments in response to MC activation; no reproducible trend of either an increased or decreased production o f each MMP over control values was evident. Each MMP initially appeare d as an inactive precursor form; collagenase 1 and stromelysin 1 were more effectively processed to active forms in the MC activated culture s. Immunolocalisation studies of MC activated explants showed that are as of extracellular tryptase were commonly associated with the local p roduction of both collagenase 1 and stromelysin 1. Conclusion-MG degra nulation induced artificially in rheumatoid synovial explant cultures consistently resulted in an increased production of PGE, but had varia ble effects on the quantification of released collagenase 1, gelatinas e A, and stromelysin 1. Such observations support the concept that act ivated synovial MCs within their native environment stimulate the prod uction of non-MG derived PGE, and may contribute to the regulation and processing of specific MMPs; both aspects represent important compone nts of the inflammatory and degradative processes of the rheumatoid le sion.