Fractalkine, a novel chemokine in rheumatoid arthritis and in rat adjuvant-induced arthritis

Objective. To examine the expression of the novel CX3C chemokine fractalkin e (Fkn) and its receptor (CX(3)CR1) in rheumatoid arthritis (RA) and rat ad juvant-induced arthritis (AIA), a model of RA. Methods. Immunohistochemistry, flow cytometry, enzyme-linked immunosorbent assay (ELISA), reverse transcriptase-polymerase chain reaction (RT-PCR), an d chemotaxis assays were used. Results. In rat AIA, synovial tissue (ST) macrophages, fibroblasts, endothe lial cells, and dendritic cells were Fkn immunopositive, whereas lymphocyte s did not significantly express Fkn. Significant staining for CX(3)CR1 was found in ST macrophages, fibroblasts, and dendritic cells, whereas only a s mall percentage of endothelial cells stained for CX(3)CR1 in rat AIA. We im munolocalized Fkn to RA ST macrophages, fibroblasts, endothelial cells, and dendritic cells. We also found intense ST macrophage and dendritic cell st aining for CX(3)CR1 in RA ST. Flow cytometry analysis of RA synovial fluid (SF) and peripheral blood revealed a greater percentage of monocytes expres sing Fkn and CX(3)CR1 compared with T cells. By ELISA, we found significant ly elevated soluble Fkn (sFkn) levels in RA SF compared with SF from patien ts with osteoarthritis or other forms of arthritis. By RT-PCR, we found enh anced expression of Fkn and CX(3)CR1 mRNA on day 18 in rat AIA, a time of p ronounced inflammation in the rat joint. Soluble Fkn-depleted RA SF showed significantly decreased chemotactic activity for monocytes compared with sh am-depleted RA SF. Conclusion. These results indicate that Fkn and its receptor are both expre ssed in RA and in rat AIA, and that sFkn is up-regulated in RA SF. Furtherm ore, our data suggest a new role for Fkn in monocyte chemotaxis in the infl amed RA joint.