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.
Highlights
Macrophages are a functionally heterogeneous cell population and depending on microenvironments they polarize in two main groups: M1 and M2
At first, we evaluated the ability of cells to release IL-10 and nitric oxide after LPS and glutamate treatments (Fig. 2)
We have found that RAW-mGluR5, without LPS stimulation, released more IL-10 (Fig. 2b) than control nontransformed cells, while the amount of secreted nitric oxide did not change significantly (Fig. 2a). 40 μM glutamate that corresponds to a concentration of glutamate in blood plasma has no effect on IL-10 release, secretion of NO or the viability of cells (24 h incubation, data not shown)
Summary
Macrophages are a functionally heterogeneous cell population and depending on microenvironments they polarize in two main groups: M1 and M2. Immune cells release amino acid glutamate (Glu) that induces chemotaxis and regulates endothelial barrier function [3, 4]. At least two uptake systems are responsible for transporting glutamate into immune cells: the excitatory amino acid transporters (EAAT) and the cystine/glutamate exchanger (xCT). EAAT-mediated glutamate uptake enables a high glutamate concentration gradient to be maintained through the cell membrane, even if extracellular glutamate concentration rises.
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