ROLE OF FC-GAMMA RECEPTORS IN THE ACTIVATION OF NEUTROPHILS BY SOLUBLE AND INSOLUBLE IMMUNOGLOBULIN AGGREGATES ISOLATED FROM THE SYNOVIAL-FLUID OF PATIENTS WITH RHEUMATOID-ARTHRITIS

Objectives-Synovial fluid from patients with rheumatoid arthritis cont ains both soluble and insoluble immunoglobulin aggregates which activa te reactive oxidant production in human neutrophils. The objectives we re to determine the roles played by Fc gamma receptors in activation o f neutrophils by these complexes. Methods-Pronase treatment was used t o remove Fc gamma RIII from the neutrophil surface and blocking monocl onal antibodies were used to prevent the binding of complexes to Fc ga mma RII and Fc gamma RIII. Results-When Fc gamma RIII from the cell su rface treatment, aggregates did not occur [mean (SD) inhibition 89 (16 )%, n = 6] whereas activation via the insoluble aggregates was less af fected [34 (16)%, n = 6]. Blocking the binding to Fc gamma RIII with a ntibodies decreased activation in response to the soluble aggregates [ mean (SD) inhibition 71 (22)%, n = 8] but again had a lower effect on activation by the insoluble aggregates [40 (17)%, n = 9]. When binding to Fc gamma RII was blocked, activation via the soluble aggregates wa s substantially inhibited [mean (SD) 93 (13)%, n = 8] whereas that via the insoluble aggregates was inhibited to a much lesser extent [28 (3 8)%, n = 9]. When Fc gamma RII and III were simultaneously blocked, ac tivation by the insoluble aggregates was only inhibited by 45% [(19), n = 5]. Conclusion-These data thus indicate that activation of human n eutrophils by soluble immunoglobulin aggregates from rheumatoid synovi al fluid occurs via cooperative occupancy of both Fc gamma RII and III : perturbation of binding to either of these receptor classes will abr ogate activation.