Abstract
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.
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Selected References
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- Berke G., Amos D. B. Mechanism of lymphocyte-mediated cytolysis. The LMC cycle and its role in transplantation immunity. Transplant Rev. 1973;17(0):71–107. doi: 10.1111/j.1600-065x.1973.tb00124.x. [DOI] [PubMed] [Google Scholar]
- Bubbers J. E., Henney C. S. Studies on the mechanism of lymphocyte-mediated cytolysis. V. The use of cytochalasins A and B to dissociate glucose transport from the lytic event. J Immunol. 1975 Jul;115(1):145–149. [PubMed] [Google Scholar]
- CRANE R. K., FIELD R. A., CORI C. F. Studies of tissue permeability. I. The penetration of sugars into the Ehrlich ascites tumor cells. J Biol Chem. 1957 Feb;224(2):649–662. [PubMed] [Google Scholar]
- Cerottini J. C., Engers H. D., Macdonald H. R., Brunner T. Generation of cytotoxic T lymphocytes in vitro. I. Response of normal and immune mouse spleen cells in mixed leukocyte cultures. J Exp Med. 1974 Sep 1;140(3):703–717. doi: 10.1084/jem.140.3.703. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen M., Whistler R. L. Action of 5-thio-D-glucose and its 1-phosphate with hexokinase and phosphoglucomutase. Arch Biochem Biophys. 1975 Aug;169(2):392–396. doi: 10.1016/0003-9861(75)90180-0. [DOI] [PubMed] [Google Scholar]
- Henney C. S. On the mechanism of T-cell mediated cytolysis. Transplant Rev. 1973;17(0):37–70. doi: 10.1111/j.1600-065x.1973.tb00123.x. [DOI] [PubMed] [Google Scholar]
- Johnson B. F. Lysis of yeast cell walls induced by 2-deoxyglucose at their sites of glucan synthesis. J Bacteriol. 1968 Mar;95(3):1169–1172. doi: 10.1128/jb.95.3.1169-1172.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaliner M., Austen K. F. Cyclic AMP, ATP, and reversed anaphylactic histamine release from rat mast cells. J Immunol. 1974 Feb;112(2):664–674. [PubMed] [Google Scholar]
- Kaluza G., Schmidt M. F., Scholtissek C. Effect of 2-deoxy-D-glucose on the multiplication of Semliki Forest virus and the reversal of the block by mannose. Virology. 1973 Jul;54(1):179–189. doi: 10.1016/0042-6822(73)90127-x. [DOI] [PubMed] [Google Scholar]
- Klenk H. D., Scholtissek C., Rott R. Inhibition of glycoprotein biosynthesis of influenza virus by D-glucosamine and 2-deoxy-D-glucose. Virology. 1972 Sep;49(3):723–734. doi: 10.1016/0042-6822(72)90529-6. [DOI] [PubMed] [Google Scholar]
- Lichtenstein L. M., DeBernardo R. The immediate allergic response: in vitro action of cyclic AMP-active and other drugs on the two stages of histamine release. J Immunol. 1971 Oct;107(4):1131–1136. [PubMed] [Google Scholar]
- MacDonald H. R., Koch C. J. Energy metabolism and T-cell-mediated cytolysis. I. Synergism between inhibitors of respiration and glycolysis. J Exp Med. 1977 Sep 1;146(3):698–709. doi: 10.1084/jem.146.3.698. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Michl J., Ohlbaum D. J., Silverstein S. C. 2-Deoxyglucose selectively inhibits Fc and complement receptor-mediated phagocytosis in mouse peritoneal macrophages II. Dissociation of the inhibitory effects of 2-deoxyglucose on phagocytosis and ATP generation. J Exp Med. 1976 Dec 1;144(6):1484–1493. doi: 10.1084/jem.144.6.1484. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Michl J., Ohlbaum D. J., Silverstein S. C. 2-Deoxyglucose selectively inhibits Fc and complement receptor-mediated phagocytosis in mouse peritoneal macrophages. I. Description of the inhibitory effect. J Exp Med. 1976 Dec 1;144(6):1465–1483. doi: 10.1084/jem.144.6.1465. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Plagemann P. G., Richey D. P. Transport of nucleosides, nucleic acid bases, choline and glucose by animal cells in culture. Biochim Biophys Acta. 1974 Dec 16;344(3-4):263–305. doi: 10.1016/0304-4157(74)90010-0. [DOI] [PubMed] [Google Scholar]
- Schmidt M. F., Schwarz R. T., Scholtissek C. Nucleoside-diphosphate derivatives of 2-deoxy-D-glucose in animal cells. Eur J Biochem. 1974 Nov 1;49(1):237–247. doi: 10.1111/j.1432-1033.1974.tb03828.x. [DOI] [PubMed] [Google Scholar]
- Steiner S., Courtney R. J., Melnick J. L. Incorporation of 2-deoxy-D-glucose into glucoproteins of normal and Simian virus 40-transformed hamster cells. Cancer Res. 1973 Oct;33(10):2402–2407. [PubMed] [Google Scholar]
- Steiner S., Steiner M. R. Incorporation of 2-deoxy-D-glucose into glycolipids of normal and SV40-transformed hamster cells. Biochim Biophys Acta. 1973 Feb 14;296(2):403–410. doi: 10.1016/0005-2760(73)90098-2. [DOI] [PubMed] [Google Scholar]