Gangliosides Produced by a T Cell Lymphoma Inhibit the Production of Reactive Nitrogen Intermediates by Murine Peritoneal Macrophages

Abstract

Dalton's lymphoma (DL), a spontaneous T cell lymphoma of mice, has been shown to inhibit macrophage activation in vitro. The present investigations were undertaken to study the mechanism of the DL-mediated macrophage inhibition. Reactive nitrogen intermediates (RNI) production of lipopolysaccharide (LPS)-treated macrophages could be reversed by the co-presence of a DL cell membrane preparation in the incubation mixture. One of the active macrophage inhibiting molecules of the DL cells was found to be the gangliosides. Incubation of macrophages with DL gangliosides (DLG) in vitro could inhibit the RNI production. DLG was found to act only at the initial stages of the LPS activation. Addition of DLG beyond 3h after the start of LPS treatment had no effect, showing that the DLG acted by altering some of the early events of the macrophage activation mechanism. In vivo administration of DLG also caused inhibition of RNI production of the macrophages. The DLG treatment was found to augment the proliferation of splenocytes by inhibiting the RNI production of the splenic macrophages. Indomethacin-treated DL cells were not significantly different from the untreated ones regarding their effect on the RNI production of macrophages, thus ruling out the involvement of metabolites of the arachidonate pathway in the modulation of macrophage activation by the DL cells.