IMMUNOCYTOCHEMICAL IDENTIFICATION OF METALLOTHIONEIN-POSITIVE CELLS IN RHEUMATOID SYNOVIUM AND ANALYSIS OF THEIR CELL LINEAGE

Metallothionein is a ubiquitous low molecular weight metalloprotein wi th powerful protective properties against oxygen radical-mediated cyto toxicity associated with inflammatory processes. In rheumatoid arthrit is, the inflammatory damage to the synovium appears to be mediated by free radicals released by the high concentration of neutrophils found in the synovial fluid of the inflamed joint. Synovial tissue obtained during routine surgery on rheumatoid and non-rheumatoid joints was sub jected to an indirect immunoperoxidase protocol for the immunolocaliza tion of metallothionein using mouse monoclonal anti-metallothionein an tibody E9, reactive against the two major isoforms of mammalian metall othionein. A layer of large dendritic-like cells situated subsynoviall y in the rheumatoid synovium stained very positively for the metallopr otein, both cytoplasmically and in their nuclei. These cells were not found in non-rheumatoid osteoarthritic or in undamaged synovial tissue associated with traumatic joint injury. An attempt was made to invest igate their lineage using a series of antibody markers against epithel ial cells, endothelial cells, smooth muscle, mesothelial cells, fibrob lasts, neutrophils, dermal dendrocytes, macrophages, low and high mole cular weight cytokeratin as well as a cell proliferation marker. From our results, it is suggested that these metallothionein-positive cells are probably myofibroblasts similar to the highly motile cells presen t in granulation tissue. They may originate from perivascular areas of synovium and their movement into the inflamed synovium may reflect th e cytoprotective role of metallothionein acting as a free radical scav enger against oxidative damage.