Activation of human polymorphonuclear neutrophil functions by interferon-gamma and tumor necrosis factors.
Recombinant human interferon-gamma (rHuIFN-gamma) and natural human tumor necrosis factor beta (nHuTNF-beta) (previously called lymphotoxin), purified to homogeneity, were used to assess their effects on certain functions of human polymorphonuclear neutrophils (PMN) in vitro. The treatment of PMN with 100 U of either rHuIFN-gamma or nHuTNF-beta for 20 min significantly increased their ability to phagocytize 1.5-microns latex beads as detected by flow cytometry. Preparations of recombinant human TNF-beta (rHuTNF-beta) showed activities similar to those of its natural counterpart in activating phagocytosis. In addition, a significant enhancement in PMN-mediated antibody-dependent cellular cytotoxicity was observed after treatment for 2 hr with IFN gamma and both TNF-alpha and TNF-beta. The enhancement by treatment with a combination of rHuIFN-gamma and nHuTNF-beta exceeded the enhancement caused by either agent alone. We also show that although lipopolysaccharide (LPS) is a potent stimulator of PMN function, polymyxin B can block LPS-induced but not lymphokine-induced activation. These data demonstrate new activities for both TNF-alpha and TNF-beta in augmenting the phagocytic and cytotoxic activities of PMN.
D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D004274:DNA, Recombinant; D006023:Glycoproteins / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008222:Lymphokines / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D010587:Phagocytosis / Q000187:drug effects; D011112:Polymyxin B / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha
D004274:DNA, Recombinant; D006023:Glycoproteins; D006131:Growth Inhibitors; D008070:Lipopolysaccharides; D008222:Lymphokines; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D011112:Polymyxin B