Synergism of 3-deazaadenosine with some Fc receptor ligands in the inhibition of antibody-dependent phagocytosis

Inhibition of phagocytosis by 3-deazaadenosine, present in vitro during the assay, is unique in that it is dependent on the concentration of IgG on Ig-coated erythrocyte target cells. This regulatory interaction is now further examined utilizing the capacity of other Fc receptor ligands, like soluble immune complexes and Ig preparations, to modulate the effect of 3-deazaadenosine on antibody-dependent phagocytosis (AD phi) in mouse resident peritoneal macrophages. Non-inhibitory concentrations of soluble immune complexes formed in mixtures of ovalbumin (OVA) antigen and rabbit anti-OVA (RAOVA) antibodies enhanced the inhibition by 3-deazaadenosine of AD phi. The effect was reversed by using F(ab')2 antibodies, that lack the Fc portion of IgG, in OVA/RAOVA mixtures. Similar synergistic effects were achieved with human gammaglobulin and IgG preparations, and were further enhanced by aggregated IgG. Another source of Fc receptor ligands, autoimmune MRL/Mp-lpr/lpr mouse sera, unlike MRL/Mp-+/+ sera, also showed synergism with 3-deazaadenosine in the inhibition of AD phi. This effect was reversed by treatment of MRL sera with F(ab')2 fragments of an anti-mouse Fc antibody. It has been pointed out that the regulatory interaction between Fc receptor ligands, like Ig-coated cells, soluble immune complexes, Ig aggregates, on one hand, and the effects of 3-deazaadenosine, on the other hand, may represent a novel mechanism by which an agent inhibits phagocytosis indirectly, by manipulating the competition among these various ligands for the macrophage Fc receptor.