TY - JOUR
T1 - Glutamate modulation of human lymphocyte growth
T2 - In vitro studies
AU - Lombardi, Grazia
AU - Miglio, Gianluca
AU - Dianzani, Chiara
AU - Mesturini, Riccardo
AU - Varsaldi, Federica
AU - Chiocchetti, Annalisa
AU - Dianzani, Umberto
AU - Fantozzi, Roberto
N1 - Funding Information:
This work was supported by Eastern Piedmont University (Vercelli, Italy), “Ministero dell’Istruzione, dell’Università e della Ricerca” (Rome, Italy), and Fondazione CARIPLO (Milan, Italy).
PY - 2004/5/28
Y1 - 2004/5/28
N2 - 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-γ (+44.3±8.2%) and IL-10 (+31.6±9.7%) secretion, whereas that of IL-2, IL-4, IL-5, and TNF-α 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.
AB - 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-γ (+44.3±8.2%) and IL-10 (+31.6±9.7%) secretion, whereas that of IL-2, IL-4, IL-5, and TNF-α 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.
KW - Excitatory amino acids
KW - IL-10
KW - INF-γ
KW - T cell proliferation
KW - Thiol-related compounds
UR - https://www.scopus.com/pages/publications/2142753016
U2 - 10.1016/j.bbrc.2004.04.053
DO - 10.1016/j.bbrc.2004.04.053
M3 - Article
SN - 0006-291X
VL - 318
SP - 496
EP - 502
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -