Energy metabolism and T-cell-mediated cytolysis. II. Selective inhibition of cytolysis by 2-deoxy-D-glucose.
The effect of the hexose analogue 2-deoxy-D-glucose (2-DG) on T-cell-mediated cytolysis has been investigated. 2-DG inhibited cytolysis in glucose-free medium but not in medium containing equimolar concentrations of glucose. This inhibition was reversible and quantitatively competitive with glucose. Among other natural sugars examined, only mannose competed effectively with 2-DG and reversed the inhibition of cytolysis, whereas sodium pyruvate, fructose, galactose, fucose, and glucosamine were without effect. Mannose and glucose were equally effective in competing with 2-DG on a molar basis. When other glucose analogues such as 5-thio-D-glucose (5-SH-G) and 3-O-methylglucose were investigated under the same conditions, no inhibition of cytolysis was observed however, 5-SH-G (but not 3-O-methylglucose) was able to reverse the inhibitory effect of 2-DG in a competitive fashion. Taken together with the data presented in the accompanying paper, these findings provide strong evidence that 2-DG inhibits T-cell-mediated cytolysis by a mechanism that is unrelated to energy production. The possibility that inhibition is related to interference with membrane glycoprotein synthesis is discussed.
D000818:Animals; D001667:Binding, Competitive; D003601:Cytotoxicity Tests, Immunologic; D003837:Deoxy Sugars / Q000494:pharmacology*; D003847:Deoxyglucose / Q000494:pharmacology*; D005632:Fructose / Q000494:pharmacology; D005643:Fucose / Q000494:pharmacology; D005690:Galactose / Q000494:pharmacology; D005944:Glucosamine / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D008358:Mannose / Q000494:pharmacology; D008757:Methylglucosides / Q000494:pharmacology; D051379:Mice; D011773:Pyruvates / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D003837:Deoxy Sugars; D008757:Methylglucosides; D011773:Pyruvates; D005643:Fucose; D005632:Fructose; D003847:Deoxyglucose; D005947:Glucose; D005944:Glucosamine; D008358:Mannose; D005690:Galactose