Activation of rat synovium by iron

We observed a consistent sequence of activation changes in rat knee synovia following a single intravenous injection of sterile ferric citrate at a dosage sufficient to cause a transient saturation of transferrin. The initial alteration, appreciated 2 hours postinjection, consisted of an expansion in the lumen of synovial lining and subsynovial tissue due to the hypervascularity and increased cellularity was noted, along with peaks in the mitotic activity of synovial cells (fourfold over baseline) and pinocytosis by endothelial cells. During the period of 8-24 hours, mature collagen appeared in the space between pericyte layers and between pericytes and endothelial cells, and 2-9-fold increases in ferritin +, W3/13+, W3/25+, Ox8+, and Ox26+ mononuclear cells occurred. In contrast to the action on synovial fibroblasts, iron injection did not affect the mitotic activity of fibroblasts within the serosa of the small intestine. These findings demonstrate that, under experimental conditions, iron can readily induce changes in the synovium that are reminiscent of early events occurring in response to antigen.