Role of 2-deoxy-D-glucose in the inhibition of phagocytosis by mouse peritoneal macrophage

Abstract

2-Deoxy-D-glucose inhibits Fc and complement receptor-mediated phagocytosis of mouse peritoneal macrophages. To understand the mechanism of this inhibition, we analyzed the 2-deoxy-D-glucose metabolites in macrophages under phagocytosis inhibition conditions and conditions of phagocytosis reversal caused by glucose, mannose and 5-thio-D-glucose, and compared their accumulations under these conditions. Macrophages metabolized 2-deoxy-D-glucose to form 2-deoxy-D-glucose 6-phosphate, 2-deoxy-D-glucose 1-phosphate, UDP-2-deoxy-D-glucose, 2-deoxy-D-glucose 1, 6-diphosphate, 2-deoxy-D-gluconic acid and 2-deoxy-6-phospho-D-gluconic acid. The level of bulk accumulation as well as the accumulation of any of these 2-deoxy-D-glucose metabolites did not correlate with changes in macrophage phagocytosis capacities caused by the reversing sugars. 2-Deoxy-D-glucose inhibited glycosylation of thioglycolate-elicited macrophage by 70-80%. This inhibition did not cause phagocytosis inhibition, since (1) the reversal of phagocytosis by 5-thio-D-glucose was not followed by increases in the incorporation of radiolabelled galactose, glucosamine, N-acetylgalactosamine or fucose; (2) cycloheximide at a concentration that inhibited glycosylation by 70-80% did not affect macrophage phagocytosis. The inhibition of protein synthesis by 2-deoxy-D-glucose similarly could not account for phagocytosis inhibition, since cycloheximide, when used at a concentration that inhibited protein synthesis by 95%, did not affect phagocytosis. 2-Deoxy-D-glucose lowered cellular nucleoside triphosphates by 70-99%, but their intracellular levels in the presence of different reversing sugars did not correlate with the magnitude of phagocytosis reversal caused by these sugars. The results show that 2-deoxy-D-glucose inhibits phagocytosis by a mechanism distinct from its usual action of inhibiting glycosylation, protein synthesis and depleting energy supplies, mechanisms by which 2-deoxy-D-glucose inhibits other cellular processes.