Augmentation of antibody-dependent cellular cytotoxicity of polymorphonuclear leukocytes by interferon-gamma: mechanism dependent on enhancement of Fc receptor expression and increased release of activated oxygens.

Abstract

The effect of recombinant human interferon (IFN) -gamma (Met-Gln form), having the same amino acid sequence as that of natural human IFN-gamma except for the N-terminal Met residue, on antibody-dependent cellular cytotoxic (ADCC) activity of human peripheral polymorphonuclear leukocytes (PMNs) against anti-chicken red blood cell (CRBC) immunoglobulin G (IgG) -coated CRBC was investigated comparatively with those of natural human IFN-alpha and -beta in vitro. IFN-gamma dramatically induced the ADCC activity at all doses tested when examined at a 1/104 dilution rate of the IgG, while no significant induction was observed with IFN-alpha or-beta. The Fc receptor (FcR) analysis by flow cytometry using fluorescein isothiocyanate-labelled (FITC) -anti-CRBC IgG revealed that IFN-gamma but not IFN-alpha or-beta remarkably increased the number of PMNs bearing FcR. By applying an in vitro measurement system for activated oxygen species using luminol solution, it was demonstrated that activated oxygen species were actually released from PMNs in the ADCC reaction. Further, inhibition experiments using three oxygen scavengers (superoxide dismutase, catalase and dimethyl sulfoxide) demonstrated the involvement of superoxide anion and hydroxy radical as cytolytic mediators in the PMN-ADCC activity induced by IFN-gamma.These results indicate a much more potent PMN-activating ability of IFN-gamma than IFN-alpha or-beta and involvement of a mechanism dependent on the enhancement of FcR expression on the PMN surface and the increased release of superoxide anions and hydroxy radicals in the PMN-ADCC augmentation by IFN-gamma.