Human monocytes tumoricidal activity: the role of interferon-gamma and bacterial lipopolysaccharide in its stimulation, preservation and decay.
The effect of interferon-gamma (IFN-gamma) and bacterial lipopolysaccharide (LPS) on the cytotoxic activity of cultured monocytes was studied in a 6-h51Cr release assay with Actinomycin-D-treated tumor cells as targets. In this system, the lysis of target cells is mediated by a soluble factor (CF) which is similar or identical to human tumor necrosis factor (TNF). The spontaneous cytotoxic activity of freshly isolated monocytes declined after their maturation to macrophages during in vitro culturing. The decrease in the ability of cultured monocytes to lyse the targets is explained by a decrease in their ability to produce the soluble cytolytic factor. Both LPS and IFN-gamma modulated the effect of culturing. LPS exhibited a dual effect. Within 2-3 h after its addition, LPS enhanced the cytotoxic activity of monocytes by increasing the synthesis of CF. However, upon a longer incubation, the decay of the activity was more pronounced in the presence of LPS. IFN-gamma did not augment the cytotoxic activity of monocytes above the basal level, yet it prevented the loss of activity which accompanies the process of monocyte maturation to macrophages.
D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D007371:Interferon-gamma / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000276:immunology
D004731:Endotoxins; D007371:Interferon-gamma