Immunohistochemical localization of metallothionein in synovial tissue of patients with chronic inflammatory and degenerative joint disease.

Metallothioneins (MTs) are low-molecular-weight cytosolic proteins, which are thought to participate in metal homeostasis and protection against metal toxicity and oxidative stress. MT synthesis can be induced by a variety of inflammatory mediators and antirheumatic drugs, and high levels of MT have been implicated in resistance of cells to some antirheumatic drugs. We studied the expression and localization of MT in synovial tissue samples from patients with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis or osteoarthritis (OA) by quantitative immunohistochemistry. Immunostaining for MT was detected in a large number of intimal lining cells in most of the investigated synovial tissue samples (75%). In a smaller proportion of samples (42%), some of the fibroblast-like cells of the subsynovial layer were also MT positive. Immunostaining and double-staining experiments with antibodies against monocyte-, macrophage- and leucocyte-associated antigens suggested that most of the MT-positive cells were intimal fibroblast-like cells and subsynovial fibroblasts. However, there were no statistically significant differences in the intensity of staining for MT between the rheumatic diseases and OA at the single-cell level. Thus, MT is expressed in synovial tissue and may participate in homeostatic and protective functions. The interindividual variability in the expression of MT in synovial tissue may be related to the therapeutic efficacy of the gold compounds and chemotherapeutic antirheumatic drugs sequestered by MT.