IFN‐γ Inhibits Internalization of Soluble Aminated β‐1, 3‐D‐Glucan by Macrophages and Thereby Down‐Regulates the Glucan Induced Release of TNF‐α: and IL‐1β

We have previously shown that soluble aminated β‐1, 3‐D‐glucan (AG) and glucan‐derivatized micro‐beads (GDM) bind to the specific β‐glucan receptor on mouse peritoneal macrophages. Phagocytosis of GDM by macrophages is mediated through the β‐glucan receptor. IFN‐γ which increases macrophage phagocytic capacity, also increased the phagocytosis of GDM. In the present study we show that IFN‐γ inhibits Internalization of AG in macrophages in a dose‐ and time‐dependent manner. The inhibitory effect of IFN‐γ was neutralized by treatment of the macrophages with cycloheximide. These results were confirmed by confocal laser scanning microscopy which showed that IFN‐7 treated cells incorporated less fluorescein‐labelled AG than did untreated cells. IFN‐γ did not change the macrophage‐binding capacity for AG showing that the inhibitory effect of IFN‐γ is not caused by decreased number of β‐glucan receptors on the cells. The stimulatory effect of AG on IL‐β and TNF‐α release from macrophages was reduced by pretreatment of the cells with IFN‐γ. We conclude that the uptake of AG and GDM in macrophages, both mediated through the β‐glucan receptor, are differently regulated by IFN‐γ. The reduced internalization of AG after IFN‐γ treatment of macrophages, is probably responsible for the down‐regulation of IL‐1 and TNF‐α secretion.