Inhibition of human natural killer activity by 2-deoxy-D-glucose and other sugars

The specificity of natural killer (NK) cells is still a matter of debate. In the present study a number of sugars were tested for their capacity to inhibit the NK activity of human peripheral blood lymphocytes (PBL) on K-562 target cells. The most pronounced inhibitory effect was exerted by 2-deoxy-D-glucose and 2-amino-D-glucose. Significant, though more variable inhibition was observed with D-fucose, D-ribose, L-rhamnose, and galactose. The inhibitory activity of the sugars was similar in NK assays carried out with target cells grown either in fetal calf serum or in normal human serum. 2-deoxy-D-glucose and 2-amino-D-glucose were shown to exert their inhibitory activity on effector rather than on target cells. They inhibited to a similar extent the NK activity of both unstimulated and interferon stimulated PBL. These 2 sugars also attenuated the antibody-dependent cell mediated cytotoxicity of PBL. The inhibitory effect of 2-deoxy-D-glucose and 2-amino-D-glucose on NK activity was not reversed by simultaneous exposure of NK cells to these inhibitors and glucose. The inhibitory effect of various sugars could result from the blocking of receptors on NK cells which recognize carbohydrate moieties on target cells. The activity of 2-deoxy-D-glucose and 2-amino-D-glucose could reflect impairment of the glycolytic pathway in the effector cells by the intracellular accumulation of phosphorylated derivatives of these inhibitors.