HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ganor, Y. Articles by Levite, M. Search for Related Content PubMed PubMed Citation Articles by Ganor, Y. Articles by Levite, M. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB GLUTAMIC ACID HYDROCHLORIDE

Human T Cells Express a Functional Ionotropic Glutamate Receptor GluR3, and Glutamate by Itself Triggers Integrin-Mediated Adhesion to Laminin and Fibronectin and Chemotactic Migration¹

Yonatan Ganor^2,*, Michal Besser^2,*,, Naomie Ben-Zakay^*, Tamar Unger^* and Mia Levite^3,*,

^* Weizmann Institute of Science, Rehovot, Israel; and Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel

T cells may encounter glutamate, the major excitatory neurotransmitter in the nervous system, when patrolling the brain and in glutamate-rich peripheral organs. Moreover, glutamate levels increase in the CNS in many pathological conditions in which T cells exert either beneficial or detrimental effects. We discovered that normal human T cells, human T leukemia cells, and mouse anti-myelin basic protein T cells express high levels of glutamate ion channel receptor (ionotropic) of -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtype 3 (GluR3). The evidence for GluR3 on T cells includes GluR3-specific RT-PCR, Western blot, immunocytochemical staining and flow cytometry. Sequencing showed that the T cell-expressed GluR3 is identical with the brain GluR3. Glutamate (10 nM), in the absence of any additional molecule, triggered T cell function: integrin-mediated T cell adhesion to laminin and fibronectin, a function normally performed by activated T cells only. The effect of glutamate was mimicked by AMPA receptor-agonists and blocked specifically by the selective receptor-antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 6-nitro-7-sulfamoylbenzo[f]quinoxalin-2,3-dione (NBQX), and by relevant anti-integrin mAbs. Glutamate also increased the CXCR4-mediated T cell chemotactic migration toward the key chemokine CXCL12/stromal cell-derived factor-1. GluR3 expression on normal, cancer and autoimmune-associated T cells and the ability of glutamate to directly activate T cell function could be of substantial scientific and clinical importance to normal neuroimmune dialogues and to CNS diseases and injury, and especially to: 1) T cell transmigration to the CNS and patrolling in the brain, 2) T cell-mediated multiple sclerosis, and 3) autoimmune epilepsy, as neurotoxic anti-GluR3 Abs are found and suspected to cause/potentiate seizures and neuropathology in several types of human epilepsies. Thus far, GluR3 was found only on neurons and glia cells; our results reveal a novel peripheral source of this antigenic receptor.

This article has been cited by other articles:

				V. Musante, F. Longordo, E. Neri, M. Pedrazzi, F. Kalfas, P. Severi, M. Raiteri, and A. Pittaluga RANTES Modulates the Release of Glutamate in Human Neocortex J. Neurosci., November 19, 2008; 28(47): 12231 - 12240. [Abstract] [Full Text] [PDF]

				I. P. Greene, E.-Y. Lee, N. Prow, B. Ngwang, and D. E. Griffin Protection from fatal viral encephalomyelitis: AMPA receptor antagonists have a direct effect on the inflammatory response to infection PNAS, March 4, 2008; 105(9): 3575 - 3580. [Abstract] [Full Text] [PDF]

				M. Levite Response to Comment on "TCR Activation Eliminates Glutamate Receptor GluR3 from the Cell Surface of Normal Human T Cells, via an Autocrine/Paracrine Granzyme B-Mediated Proteolytic Cleavage" J. Immunol., February 15, 2008; 180(4): 2007 - 2007. [Full Text] [PDF]

				Y. Ganor, V. I. Teichberg, and M. Levite TCR Activation Eliminates Glutamate Receptor GluR3 from the Cell Surface of Normal Human T Cells, via an Autocrine/Paracrine Granzyme B-Mediated Proteolytic Cleavage J. Immunol., January 15, 2007; 178(2): 683 - 692. [Abstract] [Full Text] [PDF]

				R. Pacheco, H. Oliva, J. M. Martinez-Navio, N. Climent, F. Ciruela, J. M. Gatell, T. Gallart, J. Mallol, C. Lluis, and R. Franco Glutamate Released by Dendritic Cells as a Novel Modulator of T Cell Activation J. Immunol., November 15, 2006; 177(10): 6695 - 6704. [Abstract] [Full Text] [PDF]

				C. Poulopoulou, I. Markakis, P. Davaki, C. Nikolaou, A. Poulopoulos, E. Raptis, and D. Vassilopoulos Modulation of Voltage-Gated Potassium Channels in Human T Lymphocytes by Extracellular Glutamate Mol. Pharmacol., March 1, 2005; 67(3): 856 - 867. [Abstract] [Full Text] [PDF]

				R. Pacheco, F. Ciruela, V. Casado, J. Mallol, T. Gallart, C. Lluis, and R. Franco Group I Metabotropic Glutamate Receptors Mediate a Dual Role of Glutamate in T Cell Activation J. Biol. Chem., August 6, 2004; 279(32): 33352 - 33358. [Abstract] [Full Text] [PDF]

				P. B. Sinclair, A. Sorour, M. Martineau, C. J. Harrison, W. A. Mitchell, E. O'Neill, and L. Foroni A Fluorescence in Situ Hybridization Map of 6q Deletions in Acute Lymphocytic Leukemia: Identification and Analysis of a Candidate Tumor Suppressor Gene Cancer Res., June 15, 2004; 64(12): 4089 - 4098. [Abstract] [Full Text] [PDF]

				J. R. Kanwar, R. K. Kanwar, and G. W. Krissansen Simultaneous neuroprotection and blockade of inflammation reverses autoimmune encephalomyelitis Brain, June 1, 2004; 127(6): 1313 - 1331. [Abstract] [Full Text] [PDF]