Polymorphonuclear leukocyte function triggered through the high affinity Fc receptor for monomeric IgG.
While it is extensively documented that gamma-interferon (IFN-gamma) is a potent stimulator of cells of the monocyte lineage, relatively little is known about its effects on granulocytes. We and others have found that immunoglobulin G (IgG) antibody-dependent cell cytotoxicity (ADCC) by polymorphonuclear cells (PMN) is significantly enhanced in a dose-dependent fashion by 16 hours incubation with recombinant IFN-gamma, resulting in 2- to 16-fold increases in ADCC. Incubation of PMN with lipopolysaccharide for 16 hours did not augment ADCC. Since IFN-gamma enhancement of ADCC is accompanied by increased expression of Fc receptors, we used monoclonal antibodies to compare control and IFN-gamma treated PMN for expression of the high affinity Fc receptor for monomeric IgG1 (FcgRI) and the PMN receptor for polymeric IgG (FcgR1o). Freshly isolated PMN or PMN cultured without IFN-gamma expressed FcgR1o but not detectable quantities of FcgRI. However, while FcgR1o were not increased on IFN-gamma-treated PMN, these cells expressed moderate amounts of FcgRI. To determine whether FcgRI contributed to PMN function, heteroantibodies consisting of Fab 3G8 or Fab 32 linked to Fab anti-target antibody were produced. ADCC of untreated PMN was promoted only by Fab 3G8 heteroantibody, whereas IFN-gamma-treated PMN killed through both FAB 3G8 and Fab 32 heteroantibodies. Thus, FcgRI can be induced on PMN by IFN-gamma, can mediate cytotoxicity by these cells, and probably accounts for the IFN-gamma stimulation of ADCC.
D000911:Antibodies, Monoclonal; D000920:Antibody-Dependent Cell Cytotoxicity; D002478:Cells, Cultured; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology*; D011961:Receptors, Fc / Q000502:physiology*; D017452:Receptors, IgG; D011994:Recombinant Proteins; D013329:Structure-Activity Relationship; D013997:Time Factors
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D011961:Receptors, Fc; D017452:Receptors, IgG; D011994:Recombinant Proteins; D007371:Interferon-gamma