Study of interaction between l-glutamate and human blood lymphocytes

Коstanyan, I. A.; Merkulova, Maria; Navolotskaya, E. V.; Nurieva, Roza

doi:10.1016/s0165-2478(97)00086-2

Cited by 37 publications

(23 citation statements)

References 14 publications

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“…51; and A.-C. Rimaniol and G. Gras, unpublished data). In addition, lymphocytes have glutamate receptors (52), and high glutamate concentrations depress lymphocyte function, as described in HIV infection and in patients with bronchial carcinoma (53,54). Thus, EAAT expression in peripheral macrophages should be evaluated in pathological conditions because this would make it possible to locally restrain the detrimental effects of glutamate.…”

Section: Discussionmentioning

confidence: 99%

Na+-Dependent High-Affinity Glutamate Transport in Macrophages

Rimaniol

Haı̈k

Martín

et al. 2000

The Journal of Immunology

106

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Excessive accumulation of glutamate in the CNS leads to excitotoxic neuronal damage. However, glutamate clearance is essentially mediated by astrocytes through Na+-dependent high-affinity glutamate transporters (excitatory amino acid transporters (EAATs)). Nevertheless, EAAT function was recently shown to be developmentally restricted in astrocytes and undetectable in mature astrocytes. This suggests a need for other cell types for clearing glutamate in the brain. As blood monocytes infiltrate the CNS in traumatic or inflammatory conditions, we addressed the question of whether macrophages expressed EAATs and were involved in glutamate clearance. We found that macrophages derived from human blood monocytes express both the cystine/glutamate antiporter and EAATs. Kinetic parameters were similar to those determined for neonatal astrocytes and embryonic neurons. Freshly sorted tissue macrophages did not possess EAATs, whereas cultured human spleen macrophages and cultured neonatal murine microglia did. Moreover, blood monocytes did not transport glutamate, but their stimulation with TNF-α led to functional transport. This suggests that the acquisition of these transporters by macrophages could be under the control of inflammatory molecules. Also, monocyte-derived macrophages overcame glutamate toxicity in neuron cultures by clearing this molecule. This suggests that brain-infiltrated macrophages and resident microglia may acquire EAATs and, along with astrocytes, regulate extracellular glutamate concentration. Moreover, we showed that EAATs are involved in the regulation of glutathione synthesis by providing intracellular glutamate. These observations thus offer new insight into the role of macrophages in excitotoxicity and in their response to oxidative stress.

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Section: Discussionmentioning

confidence: 99%

Na+-Dependent High-Affinity Glutamate Transport in Macrophages

Rimaniol

Haı̈k

Martín

et al. 2000

The Journal of Immunology

106

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“…Glutamate was reported to bind specific sites on T-lymphocyte plasma membranes and impair the activity of macrophages and lymphocytes in vitro (55)(56)(57). In carcinoma patients, elevated plasma glutamate levels were linked to a reduced lymphocyte response to mitogens and a high death rate (58,59).…”

Section: Analysis Of a Candidate Tumor Suppressor Gene On 6qmentioning

confidence: 99%

A Fluorescence in Situ Hybridization Map of 6q Deletions in Acute Lymphocytic Leukemia

et al. 2004

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With the objective of identifying candidate tumor suppressor genes, we used fluorescence in situ hybridization to map leukemia-related deletions of the long arm of chromosome 6 (6q). Twenty of 24 deletions overlapped to define a 4.8-Mb region of minimal deletion between markers D6S1510 and D6S1692 within chromosome 6 band q16. Using reverse transcription-PCR, we found evidence of expression in hematopoietic cells for 3 of 15 genes in the region (GRIK2, C6orf111, and CCNC). Comparison between our own and published deletion data singled out GRIK2 as the gene most frequently affected by deletions of 6q in acute lymphocytic leukemia (ALL). Sequence analysis of GRIK2 in 14 ALL cases carrying heterozygous 6q deletions revealed a constitutional and paternally inherited C to G substitution in exon 6 encoding for an amino acid change in one patient. The substitution was absent among 232 normal alleles tested, leaving open the possibility that heterozygous carriers of such mutations may be susceptible to ALL. Although low in all normal hematopoietic tissues, quantitative reverse transcription-PCR showed higher baseline GRIK2 expression in thymus and T cells than other lineages. Among T-cell ALL patients, 6q deletion was associated with a statistically significant reduction in GRIK2 expression (P ‫؍‬ 0.0001). By contrast, elevated GRIK2 expression was measured in the myelomonocytic line THP-1 and in one patient with common ALL. Finally, we detected significant levels of GRIK2 expression in prostate, kidney, trachea, and lung, raising the possibility that this gene may be protective against multiple tumor types.

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“…This binding may be due to the presence of transporters and/or specific glutamate receptors on the cell surface. The low K D value of glutamate binding and the inhibition by quisqualic acid strongly supports the presence of specific glutamate receptors of the metabotropic type (6). Among the limited number of reports on the characterization of metabotropic receptors in locations other than the nervous systems, Storto et al (7) have reported the distribution of group I and II metabotropic receptors in murine thymocytes and thymic stromal cells.…”

mentioning

confidence: 92%

Group I Metabotropic Glutamate Receptors Mediate a Dual Role of Glutamate in T Cell Activation

Pacheco

Ciruela

Casadó

et al. 2004

Journal of Biological Chemistry

124

126

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Metabotropic glutamate receptors (mGluR) are present in cells of the nervous system, where they are activated by one of the main neurotransmitters, glutamate. They are also expressed in cells outside the nervous system. We identified and characterized two receptors belonging to group I mGluR, mGlu1R and mGlu5R, in human cell lines of lymphoid origin and in resting and activated lymphocytes from human peripheral blood. Both are highly expressed in the human Jurkat T cell line, whereas mGlu5R is expressed only in the human B cell line SKW6.4. In blood lymphocytes, mGlu5R is expressed constitutively, whereas mGlu1R is expressed only upon activation via the T cell receptor-CD3 complex. Group I receptors in the central nervous system are coupled to phospholipase C, whereas in blood lymphocytes, activation of mGlu5R does not trigger this signaling pathway, but instead activates adenylate cyclase. On the other hand, mGlu5R does not mediate ERK1/2 activation, whereas mGlu1R, which is coupled neither to phospholipase C nor to calcium channels and whose activation does not increase cAMP, activates the mitogen-activated protein kinase cascade. The differential expression of mGluR in resting and activated lymphocytes and the different signaling pathways that are triggered when mGlu1Rs or mGlu5Rs are activated point to a key role of glutamate in the regulation of T cell physiological function. The study of the signaling pathways (cAMP production and ERK1/2 phosphorylation) and the proliferative response obtained in the presence of glutamate analogs suggests that mGlu1R and mGlu5R have distinct functions. mGlu5R mediates the reported inhibition of cell proliferation evoked by glutamate, which is reverted by the activation of inducible mGlu1R. This is a novel non-inhibitory action mechanism for glutamate in lymphocyte activation. mGlu1R and mGlu5R thus mediate opposite glutamate effects in human lymphocytes.There is increasing evidence that the activity of T cells in the central nervous system is regulated by neurotransmitters such as dopamine, gonadotropin-releasing hormones I and II, somatostatin, substance P, calcitonin-gene-related peptide, neuropeptide Y, and glutamate (1). The latter is the main excitatory neurotransmitter in the mammalian brain involved in learning and memory, as well as in neurotoxicity, and plays a critical role in the development and progression of diverse neurological disorders. T cells can also encounter glutamate outside the brain, in "glutamate-rich" peripheral organs such as liver, kidney, lung, muscle, and blood. It is unknown whether glutamate can be released by antigen-presenting cells, thus regulating T cell activation in the immunological synapse (2).This amino acid acts at multiple receptor types, divided into two main groups: ionotropic glutamate receptors, which form ion channels and mediate fast excitatory glutamate responses, and metabotropic glutamate receptors (mGluR), 1 which are hepta-spanning membrane-receptors and belong to the superfamily of G protein-coupled receptors (3). So f...

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Study of interaction between l-glutamate and human blood lymphocytes

Cited by 37 publications

References 14 publications

Na+-Dependent High-Affinity Glutamate Transport in Macrophages

Na+-Dependent High-Affinity Glutamate Transport in Macrophages

A Fluorescence in Situ Hybridization Map of 6q Deletions in Acute Lymphocytic Leukemia

Group I Metabotropic Glutamate Receptors Mediate a Dual Role of Glutamate in T Cell Activation

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