Activation by synergism between endotoxin and lymphokines of the mouse macrophage cell line J774 against infection by Trypanosoma cruzi.
The mouse macrophage cell line J774 was easily infected by T. cruzi epimastigotes which were transformed to amastigotes that multiplied inside the cells. Spleen-T-cells from T. cruzi immune mice stimulated with Concanavalin A or T. cruzi, but not with unrelated antigens, released lymphokines into the supernatants that when added to J774 cells were unable to induce complete trypanocidal activity, although they were able to delay the rate of infection by protecting the cells from being infected. Addition of bacterial lipopolysaccharide (LPS), although inactive by itself, acted synergistically with the supernatants in inducing complete trypanocidal activity without affecting the susceptibility of J774 cells to infection. Gamma-interferon (gamma-IFN) activity was detected in the supernatants, however, but was not solely responsible for the trypanocidal inducing activities, since: there was no correlation between the levels of gamma-IFN and macrophage activation; gamma-IFN alone was less effective than the supernatants alone; and two active fractions of 100,000-150,000 mol. wt and 30,000 mol. wt were separated by gel filtration chromatography of the lymphokine preparations. The latter, which showed the characteristics of gamma-IFN with respect to size, pH 2 sensitivity and antiviral activity, had some trypanocidal activity alone. However, the 100,000-150,000 mol. wt fraction was active only in the presence of LPS. Finally, this trypanocidal inducing activity of the supernatants was not due to the induction of synthesis of gamma-IFN by the J774 cells.
D000818:Animals; D002460:Cell Line; D003208:Concanavalin A / Q000494:pharmacology; D004357:Drug Synergism; D004731:Endotoxins / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008222:Lymphokines / Q000378:metabolism / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects*; D016215:Macrophage-Activating Factors; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D010587:Phagocytosis; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000254:growth & development / Q000276:immunology / Q000502:physiology*
D004731:Endotoxins; D008070:Lipopolysaccharides; D008222:Lymphokines; D016215:Macrophage-Activating Factors; D003208:Concanavalin A; D007371:Interferon-gamma