Modulation of intracellular glutathione concentrations alters lymphocyte activation and proliferation.
Glutathione (GSH) has been implicated in lymphocyte activation and differentiation, as well as in protection from radiation damage. Since [3H]thymidine ([3H]TdR) at high concentrations in the nucleus causes radiation damage to the cells, it is important to rule out the possibility that changes in [3H]TdR uptake by mitogen-activated lymphocytes are not caused by 3H-induced cell injury following alterations in intracellular GSH concentration. In this study, flow-cytometric analysis of cell cycle was used to measure lymphocyte activation. Intracellular GSH levels were enhanced using 2-L-oxothiazolidine-4-carboxylate (OTC) and 2-mercaptoethanol (2ME), which deliver cysteine intracellularly, and suppressed by buthionine sulfoximine (BSO) which inhibits gamma-glutamylcysteine synthetase. Enhancement of intracellular GSH concentrations in lymphocytes with 2-oxothiazolidine-4-carboxylate or 2-mercaptoethanol augments mitogen-induced lymphocyte activation, and proliferation, while suppression of intracellular GSH levels by buthionine sulfoximine inhibits the progression of cellular proliferation--but not activation, as measured by flow cytometry. There was a linear relationship between intracellular GSH concentration and conA-activated cells by flow cytometry and between GSH concentration and [3H]TdR incorporation as measured at 24 h. We conclude that alterations of intracellular GSH concentrations may be one way to modulate lymphocyte activation and differentiation.
D000165:Acridine Orange; D000818:Animals; D019328:Buthionine Sulfoximine; D002453:Cell Cycle / Q000187:drug effects*; D003208:Concanavalin A / Q000494:pharmacology; D005434:Flow Cytometry; D005978:Glutathione / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000166:cytology*; D008623:Mercaptoethanol / Q000494:pharmacology; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D011761:Pyrrolidonecarboxylic Acid; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines; D013936:Thymidine / Q000378:metabolism
D013844:Thiazoles; D053778:Thiazolidines; D003208:Concanavalin A; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D008623:Mercaptoethanol; D000165:Acridine Orange; D005978:Glutathione; D011761:Pyrrolidonecarboxylic Acid; D013936:Thymidine; C029536:2-oxothiazolidine-4-carboxylic acid