Demonstration of mast cell chemotactic activity in synovial fluid from rheumatoid patients

Objectives-The significance of the mast cell in the pathogenesis of rheumat ic diseases has become more evident. Although mast cell hyperplasia is a fe ature of rheumatoid arthritis, the nature of mast cell chemoattractants inv olved in the recruitment of mast cells in joint diseases has not been studi ed in any detail. In this study the presence of mast cell chemotactic activ ity in synovial fluids was examined. Methods-Synovial fluids from seven rheumatoid patients were tested in a mod ified Boyden chamber, where a human mast cell line was used as responder. T he presence of stem cell factor (SCF) and transforming growth factor beta ( TGF beta) was measured by enzyme linked immunosorbent assay (ELISA). Results-Six of the seven synovial fluids tested exhibited mast cell chemota ctic activity. Two characterised human mast cell chemotaxins, SCF and TGF b eta, were highly expressed in the synovium. Soluble SCF could be detected i n all fluids analysed. Blocking antibodies against SCF or TGF beta almost c ompletely blocked the activity in one fluid, partially blocked the activity in three, and did not affect the activity in two. Treatment of the respond er cells with pertussis toxin reduced the migratory response against seven fluids, indicating the presence of chemoattractants mediating their effect through G(i) coupled receptors. Conclusion-These data demonstrate the presence of multiple factors in synov ial fluid acting as mast cell chemoattractants, two of which are SCF and TG F beta that contribute to the effect. These findings may be of importance f or developing new strategies to inhibit mast cell accumulation in rheumatic diseases.