NEUTROPHILS FROM THE SYNOVIAL-FLUID OF PATIENTS WITH RHEUMATOID-ARTHRITIS EXPRESS THE HIGH-AFFINITY IMMUNOGLOBULIN-G RECEPTOR, FC-GAMMA-RI (CD64) - ROLE OF IMMUNE-COMPLEXES AND CYTOKINES IN INDUCTION OF RECEPTOR EXPRESSION

Neutrophils isolated from the synovial fluid of 16/24 patients with rh eumatoid arthritis expressed Fc gamma RI (CD64), the high-affinity rec eptor for monomeric immunoglobulin G (IgG), on their cell surface. Rec eptor expression ranged from 17% to 168% of the level of expression ob tained after incubation of control blood neutrophils with 100 U/ml int erferon-gamma (IFN-gamma) for 24 hr in vitro. Similarly, mRNA for Fc g amma RI was detected in synovial fluid neutrophils from 12/15 patients and transcript levels ranged from 5% to 200% of the values obtained a fter treatment of blood neutrophils with IFN-gamma for 4 hr in vitro. No surface expression nor mRNA were detected in freshly isolated blood neutrophils from either patients or from healthy controls. Addition o f cell-free synovial fluid to control blood neutrophils induced both m RNA and surface expression of Fc gamma RI to levels that were comparab le to those achieved after addition of IFN-gamma. Neither soluble nor insoluble immune complexes appeared to be involved in induction of Fc gamma RI expression in spite of the ability of these complexes to indu ce protein biosynthesis. Synovial fluid-induced expression of Fc gamma RI was partially blocked by incubation with neutralizing IFN-gamma an tibodies, whilst neutralizing interleukin (IL)-6 antibodies had little effect. Levels of IFN-gamma, measured within these synovial fluids ra nged from 0 to 2.7 U/ml, well within the range known to induce neutrop hil Fc gamma RI expression. These data thus indicate that gene express ion in synovial fluid neutrophils is selectively activated as the cell s enter the diseased joint. Furthermore, these data indicate that indu ced expression of Fc gamma RI may alter the ability of infiltrating ne utrophils to respond to IgG-containing immune complexes present in the se joints.