Metabotropic glutamate receptor 5 may be involved in macrophage plasticity

Abstract

BackgroundMacrophages are a functionally heterogeneous cell population and depending on microenvironments they polarize in two main groups: M1 and M2. Glutamic acid and glutamate receptors may participate in the regulation of macrophage plasticity. To investigate the role of glutamatergic systems in macrophages physiology, we performed the transfection of mGluR5 cDNAs into RAW-264.7 cells.ResultsComparative analysis of modified (RAW-mGluR5 macrophages) and non-modified macrophages (RAW-macrophages) has shown that the RAW-mGluR5 macrophages absorbed more glutamate than control cells and the amount of intracellular glutamate correlated with the expression of excitatory amino acid transporters -2 (EAAT-2). Besides, our results have shown that RAW-mGluR5 macrophages expressed a higher level of peroxisome proliferator-activated receptor γ (PPAR-γ) and secreted more IL-10, high mobility group box 1 proteins (HMGB1) and Galectin-3 than control RAW-macrophages.ConclusionsWe propose that elevation of intracellular glutamate and expression of mGluR5 may initiate the metabolic rearrangement in macrophages that could contribute to the formation of an immunosuppressive phenotype.

The role of Galectin-3 in modulating tumor growth and immunosuppression within the tumor microenvironment

“…Classical M1 macrophage activation with LPS inhibits Gal-3 expression and release, whereas alternative macrophage activation by IL-4/IL-13 leads to the accelerated biosynthesis and secretion of Gal-3, 31 , 32 suggesting that Gal-3 may be a specific and highly up-regulated marker of M2-type macrophages. 33 IL-4 mediates M2 macrophage activation and subsequently activates increased Gal-3 expression as well as other phenotypic M2 activation markers. Gal-3 then becomes part of a feedback loop for driving M2 macrophage activation by binding to CD98 or CD98 and β1 integrin complex, which leads to PI3 K activation and thus M2 activation.…”

The Glutamatergic System in Primary Somatosensory Neurons and Its Involvement in Sensory Input-Dependent Plasticity

“…The expression of these transporters and receptors is modified with the activation of these cells [ 107 , 108 , 110 ]. Recently, it has been reported that T cells in Multiple Sclerosis patients display elevated levels of GluA3 during relapse and with active disease [ 111 ], and that macrophages that do not normally express EAATs do so under inflammatory conditions [ 110 ].…”

“…The expression of these transporters and receptors is modified with the activation of these cells [ 107 , 108 , 110 ]. Recently, it has been reported that T cells in Multiple Sclerosis patients display elevated levels of GluA3 during relapse and with active disease [ 111 ], and that macrophages that do not normally express EAATs do so under inflammatory conditions [ 110 ]. In DRG or peripheral nerves, where T-cell and macrophages are present [ 112 , 113 ], no studies have examined whether GluRs are expressed by these cells, and certainly it is unknown whether they play a role in glutamate-related plasticity.…”

The Galectin Family as Molecular Targets: Hopes for Defeating Pancreatic Cancer

“…Importantly, Gal3 is involved in TCR clustering [84] and induces T-cell apoptosis via interactions with CD45 and CD71 [85]. Further, it is a marker of M2 macrophage activation [86,87] and maintains a macrophage fate by binding to CD98 and triggering PI3K activation [86]. Interestingly, in preclinical trials, Gal3 blockade in solid tumors together with PD1/PDL1 checkpoint inhibition or T-cell agonists boost an immunologic response against tumors, resulting in tumor regression [88].…”