Glutamate modulation of human lymphocyte growth: in vitro studies |
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Authors: | Lombardi Grazia Miglio Gianluca Dianzani Chiara Mesturini Riccardo Varsaldi Federica Chiocchetti Annalisa Dianzani Umberto Fantozzi Roberto |
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Affiliation: | Interdisciplinary Research Center of Autoimmune Diseases, DISCAFF Department, Eastern Piedmont University, Via Bovio 6, 28100 Novara, Italy. lombardi@pharm.unipmn.it |
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Abstract: | 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. |
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Keywords: | T cell proliferation INF-γ IL-10 Thiol-related compounds Excitatory amino acids |
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