Glycine inhibits growth of T lymphocytes by an IL-2-independent mechanism.
Previously, it was shown that glycine prevented increases in intracellular calcium ([Ca2+]i) in Kupffer cells. Since Kupffer cells and T lymphocytes are derived from the same pluripotent stem cell, it was hypothesized that glycine would prevent increases in [Ca2+]i in lymphocytes and inhibit cell proliferation. Lymphocyte proliferation was measured in one-way MLC with spleen cells from DA and Lewis rats and in enriched T lymphocyte preparations stimulated by immobilized anti-CD3 Ab. Glycine caused a dose-dependent decrease in cell proliferation to about 40% of control. Con A caused a dose-dependent increase in [Ca2+]i in Jurkat cells which was blunted maximally with 0.6 mM glycine. The effect of glycine was dependent on extracellular chloride and reversed by strychnine, an antagonist of the glycine-gated chloride channel. Similar results were obtained with rat T lymphocytes stimulated by anti-CD3 Ab. Surprisingly, glycine had no effect on IL-2 production in the mixed lymphocyte culture; therefore, the effect of glycine on IL-2-dependent proliferation was tested. Glycine and rapamycin caused dose-dependent decreases in IL-2-stimulated growth of Ctll-2 cells to about 60% and 40%, respectively, of control. Moreover, glycine also inhibited the IL-2-stimulated growth of rat splenic lymphocytes. It is concluded that glycine blunts proliferation in an IL-2-independent manner. This is consistent with the hypothesis that glycine activates a glycine-gated chloride channel and hyperpolarizes the cell membrane-blunting increases in [Ca2+]i that are required for transcription of factors necessary for cell proliferation.
Stachlewitz
R F
RF
Laboratory of Hepatobiology and Toxicology, Department of Pharmacology, University of North Carolina, Chapel Hill 27599, USA.
Li
X
X
Smith
S
S
Bunzendahl
H
H
Graves
L M
LM
Thurman
R G
RG
D000818:Animals; D017252:CD3 Complex / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D065101:Chloride Channel Agonists; D003208:Concanavalin A / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D005260:Female; D005998:Glycine / Q000819:agonists / Q000502:physiology*; D006131:Growth Inhibitors / Q000819:agonists / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007376:Interleukin-2 / Q000502:physiology*; D007424:Intracellular Fluid / Q000378:metabolism; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D051381:Rats; D011917:Rats, Inbred Lew; D013331:Strychnine / Q000819:agonists; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism
D017252:CD3 Complex; D065101:Chloride Channel Agonists; D006131:Growth Inhibitors; D007106:Immune Sera; D007376:Interleukin-2; D003208:Concanavalin A; D016572:Cyclosporine; D013331:Strychnine; D002118:Calcium; D005998:Glycine