Konopski Z, Seljelid R, Eskeland T
Department of Experimental Pathology and Anatomy, University of Tromsø, Norway.
Scand J Immunol. 1994 Jul;40(1):57-63. doi: 10.1111/j.1365-3083.1994.tb03433.x.
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.
我们之前已经表明，可溶性活性β-1,3-D-葡聚糖（AG）和葡聚糖衍生的微珠（GDM）可与小鼠腹腔巨噬细胞上的特异性β-葡聚糖受体结合。巨噬细胞对GDM的吞噬作用是通过β-葡聚糖受体介导的。可增加巨噬细胞吞噬能力的γ干扰素，也增强了对GDM的吞噬作用。在本研究中，我们发现γ干扰素以剂量和时间依赖性方式抑制巨噬细胞中AG的内化。用环己酰亚胺处理巨噬细胞可中和γ干扰素的抑制作用。共聚焦激光扫描显微镜证实了这些结果，该显微镜显示，经γ干扰素处理的细胞比未处理的细胞摄取的荧光素标记的AG更少。γ干扰素并未改变巨噬细胞对AG的结合能力，这表明γ干扰素的抑制作用不是由细胞上β-葡聚糖受体数量减少引起的。用γ干扰素预处理细胞可降低AG对巨噬细胞释放白细胞介素-1β和肿瘤坏死因子-α的刺激作用。我们得出结论，巨噬细胞中通过β-葡聚糖受体介导的AG和GDM摄取，受到γ干扰素的不同调节。γ干扰素处理巨噬细胞后AG内化减少，可能是白细胞介素-1和肿瘤坏死因子-α分泌下调的原因。
