Amino Acids

, Volume 42, Issue 1, pp 221–229 | Cite as

EAAT expression by macrophages and microglia: still more questions than answers

  • Gabriel Gras
  • Boubekeur Samah
  • Audrey Hubert
  • Cathie Léone
  • Fabrice Porcheray
  • Anne-Cécile Rimaniol
Review Article


Glutamate is the main excitatory amino acid, but its presence in the extracellular milieu has deleterious consequences. It may induce excitotoxicity and also compete with cystine for the use of the cystine–glutamate exchanger, blocking glutathione neosynthesis and inducing an oxidative stress-induced cell death. Both mechanisms are critical in the brain where up to 20% of total body oxygen consumption occurs. In normal conditions, the astrocytes ensure that extracellular concentration of glutamate is kept in the micromolar range, thanks to their coexpression of high-affinity glutamate transporters (EAATs) and glutamine synthetase (GS). Their protective function is nevertheless sensitive to situations such as oxidative stress or inflammatory processes. On the other hand, macrophages and microglia do not express EAATs and GS in physiological conditions and are the principal effector cells of brain inflammation. Since the late 1990s, a number of studies have now shown that both microglia and macrophages display inducible EAAT and GS expression, but the precise significance of this still remains poorly understood. Brain macrophages and microglia are sister cells but yet display differences. Both are highly sensitive to their microenvironment and can perform a variety of functions that may oppose each other. However, in the very particular environment of the healthy brain, they are maintained in a repressed state. The aim of this review is to present the current state of knowledge on brain macrophages and microglial cells activation, in order to help clarify their role in the regulation of glutamate under pathological conditions as well as its outcome.


Microglia Macrophage EAAT xCT Glutamate Glutathione Neuroinflammation 



Alzheimer’s disease


Astrocyte elevated gene


Blood–brain barrier


Cluster of differentiation


Central nervous system


Chemokine (C-C motif) receptor


Chemokine (C-X3-C motif) ligand


Chemokine (C-X3-C motif) receptor


Excitatory amino acid transporter


Epidermal growth factor


Fibroblast growth factor


Found in Inflammatory Zone 1, a marker of alternative activation in murine macrophages


Glutamine synthetase


l-γ-Glutamyl-l-cysteinyl-glycine (glutathione)


Oxidised form of glutathione


Human immunodeficiency virus






Immunoreceptor tyrosine-based inhibition motif


Monocyte-derived macrophages


Metabotropic glutamate receptors


Major histocompatibility complex


Nuclear factor-κB.


Platelet-derived growth factor




Signal-regulatory protein α


Simian immunodeficiency virus


Transforming growth factor


Tumour necrosis factor


Triggering receptor expressed on myeloid cells 2


Vesicular glutamate transporter


Light chain subunit of the xc cystine/glutamate exchanger


A heparin-binding lectin, a marker of alternative activation in murine macrophages


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Gabriel Gras
    • 1
  • Boubekeur Samah
    • 1
  • Audrey Hubert
    • 1
  • Cathie Léone
    • 1
  • Fabrice Porcheray
    • 1
  • Anne-Cécile Rimaniol
    • 1
  1. 1.Division of Immuno-Virology, Institute of Emerging Diseases and Innovative TherapiesUMR E1 CEA DSV/IMETI/SIV and University Paris South-Paris 11Fontenay-aux RosesFrance

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