Immune interferon enhances functional properties of human granulocytes: role of Fc receptors and effect of lymphotoxin, tumor necrosis factor, and granulocyte-macrophage colony-stimulating factor.
We report here a comparative study of the effects of several cytokines known to affect myeloid cell differentiation on functional properties of human mature granulocytes. We show that recombinant interferon-gamma (rIFN-gamma), recombinant granulocyte/macrophage-colony stimulating factor (rGM-CSF), recombinant tumor necrosis factor (rTNF), and lymphotoxin (LT) purified to homogeneity are potent stimulators of polymorphonuclear cells (PMN) activity. All cytokines enhance antibody-dependent cell-mediated cytotoxicity (Ab-CMC) mediated by human PMN; however, rGM-CSF, rTNF, and LT have an immediate and short-lived effect on the PMN, whereas the activation by rIFN-gamma requires several hours of induction but can be observed up to 24 to 48 hr of culture. Only the effect of rIFN-gamma is in part dependent on induction of a high-affinity FcR for monomeric IgG on PMN, as suggested by two-color sorting analysis, and on mechanisms that result in prolonged survival of PMN in a functionally active state to mediate oxidative burst, phagocytosis, and bactericidal activity. Greater enhancement of Ab-CMC is obtained by using rIFN-gamma in combination with the other cytokines. Our data indicate that cytokines previously defined on the basis of their cytotoxic effects mediate a wide spectrum of activities on mature myeloid cells and provide evidence for their possible role in vivo, alone or in combination with rIFN-gamma, in modulating functional activities of cells responsible for non-adaptive systems of defense.
D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D007371:Interferon-gamma / Q000494:pharmacology; D007377:Interleukin-3; D008214:Lymphocytes / Q000187:drug effects; D008233:Lymphotoxin-alpha / Q000494:pharmacology*; D016177:Macrophage-1 Antigen; D009000:Monocytes / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D010084:Oxidation-Reduction; D010587:Phagocytosis / Q000187:drug effects; D011951:Receptors, Complement / Q000032:analysis; D011961:Receptors, Fc / Q000032:analysis / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha
D006023:Glycoproteins; D007140:Immunoglobulin Fab Fragments; D007377:Interleukin-3; D008233:Lymphotoxin-alpha; D016177:Macrophage-1 Antigen; D011951:Receptors, Complement; D011961:Receptors, Fc; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma