Glutamate modulation of human lymphocyte growth: in vitro studies.
Peripheral blood mononuclear cell (PBMC) proliferation induced by phytohemagglutinin, or by anti-CD3 alone or plus anti-CD28 monoclonal antibodies (mAb) was inhibited by glutamate (Glu) in a concentration-dependent manner. This inhibition was not reproduced by selective ionotropic Glu receptor agonists, whereas it was potentiated by l-buthionine-(S,R)-sulfoximine, which depletes glutathione (GSH) stores, and counteracted by 2-mercaptoethanol, a preserver of cell thiols. The inhibitory effects of Glu were related to depletion of intracellular GSH stores, since it decreased GSH levels in a concentration-dependent manner. Furthermore, Glu modulated cytokine secretion by anti-CD3 mAb activated PBMC: it increased IFN-gamma (+44.3+/-8.2%) and IL-10 (+31.6+/-9.7%) secretion, whereas that of IL-2, IL-4, IL-5, and TNF-alpha was not affected. These data suggest that high levels of Glu, which can be reached in damaged tissues, modulate lymphocyte responses to activating stimuli by favouring polarization of the T helper effector response.
Lombardi
Grazia
G
Interdisciplinary Research Center of Autoimmune Diseases, DISCAFF Department, Eastern Piedmont University, Via Bovio 6, 28100 Novara, Italy. lombardi@pharm.unipmn.it
Miglio
Gianluca
G
Dianzani
Chiara
C
Mesturini
Riccardo
R
Varsaldi
Federica
F
Chiocchetti
Annalisa
A
Dianzani
Umberto
U
Fantozzi
Roberto
R
D000911:Antibodies, Monoclonal / Q000276:immunology; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005971:Glutamates / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008623:Mercaptoethanol / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D005971:Glutamates; D007378:Interleukins; D010835:Phytohemagglutinins; D014409:Tumor Necrosis Factor-alpha; D019328:Buthionine Sulfoximine; D008623:Mercaptoethanol; D007371:Interferon-gamma; D005978:Glutathione