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Published on: December 27, 2016
Glutamate modulation of human lymphocyte growth: in vitro studies
Grazia Lombardi1, Gianluca Miglio, Chiara Dianzani
1Interdisciplinary Research Center of Autoimmune Diseases, DISCAFF Department, Eastern Piedmont University, Via Bovio 6, 28100 Novara, Italy. lombardi@pharm.unipmn.it
Insights
Glutamate (Glu) inhibits peripheral blood mononuclear cell (PBMC) proliferation and alters cytokine secretion. This immune modulation is linked to glutathione (GSH) depletion, suggesting a role for Glu in damaged tissues.
Area of Science:
- Immunology
- Neuroscience
- Cell Biology
Background:
- Peripheral blood mononuclear cells (PBMC) play a crucial role in immune responses.
- Glutamate (Glu) is a key neurotransmitter but also found in tissues.
- Understanding Glu's role in immune cell function is important for inflammatory conditions.
Purpose of the Study:
- To investigate the effect of glutamate on PBMC proliferation and cytokine production.
- To elucidate the mechanism underlying glutamate's immunomodulatory effects.
Main Methods:
- PBMC proliferation assays using phytohemagglutinin and anti-CD3/anti-CD28 antibodies.
- Assessment of intracellular glutathione (GSH) levels.
- Measurement of cytokine secretion (IFN-gamma, IL-10, IL-2, IL-4, IL-5, TNF-alpha).
Main Results:
- Glutamate inhibited PBMC proliferation in a concentration-dependent manner.
- Inhibition was linked to decreased intracellular GSH levels.
- Glutamate increased IFN-gamma and IL-10 secretion, but not other tested cytokines.
Conclusions:
- High glutamate levels, as seen in damaged tissues, can modulate lymphocyte responses.
- Glutamate influences T helper cell polarization through mechanisms involving GSH depletion.
- These findings suggest a role for glutamate in regulating immune responses in pathological conditions.
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.
