IFN-gamma inhibits internalization of soluble aminated beta-1,3-D-glucan by macrophages and thereby down-regulates the glucan induced release of TNF-alpha and IL-1 beta.
We have previously shown that soluble animated beta-1,3-D-glucan (AG) and glucan-derivatized microbeads (GDM) bind to the specific beta-glucan receptor on mouse peritoneal macrophages. Phagocytosis of GDM by macrophages is mediated through the beta-glucan receptor. IFN-gamma which increases macrophage phagocytic capacity, also increased the phagocytosis of GDM. In the present study we show that IFN-gamma inhibits internalization of AG in macrophages in a dose- and time-dependent manner. The inhibitory effect of IFN-gamma was neutralized by treatment of the macrophages with cycloheximide. These results were confirmed by confocal laser scanning microscopy which showed that IFN-gamma treated cells incorporated less fluorescein-labelled AG than did untreated cells. IFN-gamma did not change the macrophage-binding capacity for AG showing that the inhibitory effect of IFN-gamma is not caused by decreased number of beta-glucan receptors on the cells. The stimulatory effect of AG on IL-1 beta and TNF-alpha release from macrophages was reduced by pretreatment of the cells with IFN-gamma. We conclude that the uptake of AG and GDM in macrophages, both mediated through the beta-glucan receptor, are differently regulated by IFN-gamma. The reduced internalization of AG after IFN-gamma treatment of macrophages, is probably responsible for the down-regulation of IL-1 and TNF-alpha secretion.
Department of Experimental Pathology and Anatomy, University of Tromsø, Norway.
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Konopski
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Seljelid
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D000818:Animals; D001667:Binding, Competitive; D015536:Down-Regulation; D005260:Female; D005936:Glucans / Q000276:immunology / Q000378:metabolism*; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000502:physiology*; D007375:Interleukin-1 / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D047071:beta-Glucans
D005936:Glucans; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D047071:beta-Glucans; D007371:Interferon-gamma; C033363:beta-1,3-glucan