Metabolic changes in activated T cells: an NMR study of human peripheral blood lymphocytes.
Using NMR spectroscopy, we studied purified, human T lymphocytes in a serum-free medium. Purified cells were entrapped inside agarose beads and induced to proliferate by the mitogens phorbol-12-myristate-13-acetate and ionomycin. T lymphocytes in standard culture and inside agarose beads exhibit comparable viability, and similar extent and kinetics of DNA synthesis and interleukin-2 secretion. 31P-NMR revealed decreased phosphomonoester and increased phosphodiester content in cells stimulated for two days or longer. 13C-glucose utilization and 13C-lactate production rates showed that 85% of the utilized glucose was converted to lactate. 1H-NMR spectra of the perfusing media indicated that lactate was also produced from substrates other than glucose or glycogen. Glucose accounted for 25% of the lactate produced by quiescent cells, and for 67% of lactate production by stimulated cells. Glycolysis was enhanced 6-fold within the first 2 hours following stimulation, and 15-fold by 48 or 96 h. Aerobic lactate production was increased 3-fold by 48 h, with only a minor enhancement during the first 12 h of stimulation. Our results indicate a shift from mostly aerobic to mostly anaerobic lactate production in T lymphocytes within the first 90 min of the G0 to G1 transition during cell cycle progression.
Bental
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Department of Physiology, University of Pennsylvania, Philadelphia 19104-6085.
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D000255:Adenosine Triphosphate / Q000378:metabolism; D002244:Carbon; D002455:Cell Division; D002470:Cell Survival; D004247:DNA / Q000096:biosynthesis; D004983:Ethanolamines / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D005971:Glutamates / Q000096:biosynthesis; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D006859:Hydrogen; D007376:Interleukin-2 / Q000378:metabolism; D007773:Lactates / Q000096:biosynthesis; D008213:Lymphocyte Activation; D009682:Magnetic Resonance Spectroscopy; D010710:Phosphates / Q000378:metabolism; D010758:Phosphorus / Q000378:metabolism; D010767:Phosphorylcholine / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism; D012685:Sepharose; D013601:T-Lymphocytes / Q000378:metabolism*
D004983:Ethanolamines; D005971:Glutamates; D007376:Interleukin-2; D007773:Lactates; D010710:Phosphates; D011773:Pyruvates; D010767:Phosphorylcholine; D010758:Phosphorus; D002244:Carbon; C005448:phosphorylethanolamine; D006859:Hydrogen; D000255:Adenosine Triphosphate; D006003:Glycogen; D004247:DNA; D012685:Sepharose; D005947:Glucose