RANTES Expression and Contribution to Monocyte Chemotaxis in Arthritis

Rheumatoid arthritis (RA) is characterized by recruitment of leukocytes from the vasculature into inflamed synovial tissue (ST) and synovial fluid (SF), which depends, in part, upon the continued maintenance of chemotactic stimuli. RANTES is a potent chemoattractant for leukocytes including monocytes and CD45RO⁺memory T lymphocytes. The aim of this study was to determine the production, the source, and the function of antigenic RANTES in arthritis. We detected antigenic RANTES in SFs from RA and OA patients (100 ± 22.7 and 72 ± 30.7 pg/ml, respectively). CM from RA ST fibroblasts stimulated with interleukin-1β or tumor necrosis factor-α contained significantly more antigenic RANTES than unstimulated CM (452 ± 181.6 and 581 ± 200.2 pg/ml, respectively, versus 12 ± 4.4 pg/ml,P< 0.05). PHA-stimulated RA SF mononuclear cells secreted 5- to 15-fold more antigenic RANTES than did nonstimulated mononuclear cells, while LPS induced secretion up to 4-fold. We immunolocalized antigenic RANTES to sublining macrophages (28 ± 3.7 and 8 ± 2.0% immunopositive cells), perivascular macrophages (56 ± 6.9 and 19 ± 3.4%), and synovial lining cells (37 ± 5.8 and 60 ± 10.4%) in RA and OA tissue, respectively. Anti-RANTES neutralized 20.2 ± 1.3% of the RA SF chemotactic activity for normal peripheral blood monocytes (P< 0.05). These results demonstrate antigenic RANTES in RA and OA ST and SF and identify RANTES as a chemoattractant for monocytes in the RA joint.