EXPRESSION OF THE C5A RECEPTOR (CD88) ON SYNOVIAL MAST-CELLS IN PATIENTS WITH RHEUMATOID-ARTHRITIS

Objective. To analyze the immunophenotype and functional properties of synovial mast cells (SyMC) in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Methods. Synovial tissue was obtained from 2 5 patients with RA and 17 patients with OA. Tissue was dispersed by en zymatic digestion using collagenase. Surface receptor expression on Sy MC was analyzed by monoclonal antibodies (MAb) and indirect immunofluo rescence staining. Histamine release experiments were performed using the MC agonist recombinant human (rHu) stem cell factor (SCF), the ana phylatoxin rHuC5a, and an anti-IgE antibody. Results. In both groups o f patients (RA and GA), SyMC were found to react with MAI, to IgE, SCF receptor (c-kit, CD117), as well as CD antigens likewise expressed in lung MC (CD9, CD29, CD33, CD43, CD44, CD45). However, a significantly increased proportion of SyMC from RA patients reacted with MAb agains t C5a receptor (C5aR; CD88), compared with SyMC from OA (mean +/- SD p ercentage of SyMC reacting with CD88 MAb S5/1 in RA 27.5 +/- 8.6% vers us 0.0% in OA, and with CD88 MAb W17/1 in RA 58.3 +/- 15.2% versus 12. 5 +/- 15.0% in OA; P < 0.05). Furthermore, in RA, significant histamin e release from SyMC above control was induced by rHuC5a, anti-IgE, and rHuSCF, whereas SyMC in OA released histamine after stimulation with anti-IgE and rHuSCF, but not rHuC5a. Conclusion. SyMC exhibit phenotyp ic and functional properties similar to MC in other tissues. In patien ts with RA,but not OA, SyMC express significant amounts of C5aR (CD88) and release histamine in response to rHuC5a. These results indicate a role for SyMC and C5a/C5aR in the pathogenesis of RA.