Macrophages treated with particulate matter PM<inf>2.5</inf> induce selective neurotoxicity through glutaminase-mediated glutamate generation

Fang Liu, Yunlong Huang, Fang Zhang, Qiang Chen, Beiqing Wu, Wei Rui, Jialin C Zheng, Wenjun Ding

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Exposure to atmospheric particulate matter PM<inf>2.5</inf> (aerodynamic diameter ≤ 2.5 μm) has been epidemiologically associated with respiratory illnesses. However, recent data have suggested that PM<inf>2.5</inf> is able to infiltrate into circulation and elicit a systemic inflammatory response. Potential adverse effects of air pollutants to the central nervous system (CNS) have raised concerns, but whether PM<inf>2.5</inf> causes neurotoxicity remains unclear. In this study, we have demonstrated that PM<inf>2.5</inf> impairs the tight junction of endothelial cells and increases permeability and monocyte transmigration across endothelial monolayer in vitro, indicating that PM<inf>2.5</inf> is able to disrupt blood-brain barrier integrity and gain access to the CNS. Exposure of primary neuronal cultures to PM<inf>2.5</inf> resulted in decrease in cell viability and loss of neuronal antigens. Furthermore, supernatants collected from PM<inf>2.5</inf>-treated macrophages and microglia were also neurotoxic. These macrophages and microglia significantly increased extracellular levels of glutamate following PM<inf>2.5</inf> exposure, which were negatively correlated with neuronal viability. Pre-treatment with NMDA receptor antagonist MK801 alleviated neuron loss, suggesting that PM<inf>2.5</inf> neurotoxicity is mediated by glutamate. To determine the potential source of excess glutamate production, we investigated glutaminase, the main enzyme for glutamate generation. Glutaminase was reduced in PM<inf>2.5</inf>-treated macrophages and increased in extracellular vesicles, suggesting that PM<inf>2.5</inf> induces glutaminase release through extracellular vesicles. In conclusion, these findings indicate PM<inf>2.5</inf> as a potential neurotoxic factor, crucial to understanding the effects of air pollution on the CNS.

Original languageEnglish (US)
Pages (from-to)315-326
Number of pages12
JournalJournal of Neurochemistry
Volume134
Issue number2
DOIs
StatePublished - Jul 1 2015

Fingerprint

Glutaminase
Particulate Matter
Macrophages
Glutamic Acid
Neurology
Central Nervous System
Microglia
Transendothelial and Transepithelial Migration
Air Pollutants
Tight Junctions
Endothelial cells
Air Pollution
N-Methyl-D-Aspartate Receptors
Blood-Brain Barrier
Air pollution
Cell culture
Neurons
Monocytes
Monolayers
Permeability

Keywords

  • blood-brain barrier
  • glutamate
  • glutaminase
  • macrophage
  • neurotoxicity
  • PM <inf>2.5</inf>

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Macrophages treated with particulate matter PM<inf>2.5</inf> induce selective neurotoxicity through glutaminase-mediated glutamate generation. / Liu, Fang; Huang, Yunlong; Zhang, Fang; Chen, Qiang; Wu, Beiqing; Rui, Wei; Zheng, Jialin C; Ding, Wenjun.

In: Journal of Neurochemistry, Vol. 134, No. 2, 01.07.2015, p. 315-326.

Research output: Contribution to journalArticle

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