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Our understanding of the role of iron in rheumatoid arthritis (RA) has improved with a recent study showing where iron accumulates in the synovial membranes of affected joints. The researchers speculate how iron might build up to toxic amounts.
Ferritin, both light and heavy subunits, was found in the lining layer and subintimal zone of the synovium and in synovial macrophages and fibroblasts. Transferrin receptor appeared only in the lining layer.
Non-specific resistance associated macrophage proteins (Nramp) were also found. These are proteins that span membranes and transport divalent cations. Nramp 2 occurred in macrophages and fibroblasts. Nramp 1 was present in macrophages and neutrophils, in the synovial lining layer and the subintimal zone, and in infiltrating inflammatory cells, but not in fibroblasts.
The study used synovial membranes from arthroplasties of 20 patients with RA. Thin sections were stained cytochemically for ferritin, transferrin receptor, and Nramp 1 with monoclonal or poylclonal antibodies. Macrophages and fibroblasts were isolated from collaginase digests of synovial membranes. Neutrophils were isolated from synovial fluid aspirated routinely from the joints. These cell types were stained for ferritin and transferrin receptor immunocytochemically. Nramp 1 and Nramp 2 were identified by reverse transcriptase polymerase chain reaction.
A high iron content has been noted in synovial membranes in RA, but the uptake and storage of iron and its potential relation to inflammation of the joints has been unknown until now.