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

Abstract

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.

Keywords

Microglia Macrophage EAAT xCT Glutamate Glutathione Neuroinflammation 

Abbreviations

AD

Alzheimer’s disease

AEG

Astrocyte elevated gene

BBB

Blood–brain barrier

CD

Cluster of differentiation

CNS

Central nervous system

CCR

Chemokine (C-C motif) receptor

CX3CL

Chemokine (C-X3-C motif) ligand

CX3CR

Chemokine (C-X3-C motif) receptor

EAAT

Excitatory amino acid transporter

EGF

Epidermal growth factor

FGF

Fibroblast growth factor

FIZZ1

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

GS

Glutamine synthetase

GSH

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

GSSG

Oxidised form of glutathione

HIV

Human immunodeficiency virus

IFN

Interferon

IL

Interleukin

ITIM

Immunoreceptor tyrosine-based inhibition motif

MDM

Monocyte-derived macrophages

mGluR

Metabotropic glutamate receptors

MHC

Major histocompatibility complex

NF-κB

Nuclear factor-κB.

PDGF

Platelet-derived growth factor

PG

Prostaglandin

SIRPα

Signal-regulatory protein α

SIV

Simian immunodeficiency virus

TGF

Transforming growth factor

TNF

Tumour necrosis factor

TREM2

Triggering receptor expressed on myeloid cells 2

VGLUT

Vesicular glutamate transporter

xCT

Light chain subunit of the xc cystine/glutamate exchanger

Ym1

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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