Macrophages treated with particulate matter PM2.5 induce selective neurotoxicity through glutaminase‐mediated glutamate generation

• DOI: 10.1111/jnc.13135
• Publication Date: 2015-04-25T06:59:02Z
• Authors: Fang Liu; Yunlong Huang; Fang Zhang; Qiang Chen; Beiqing Wu; Wei Rui; Jialin C. Zheng; Wenjun Ding
• Keywords: Neurotoxicity; Glutaminase; Viability assay

Abstract Exposure to atmospheric particulate matter PM 2.5 (aerodynamic diameter ≤ μm) has been epidemiologically associated with respiratory illnesses. However, recent data have suggested that is able infiltrate into circulation and elicit a systemic inflammatory response. Potential adverse effects of air pollutants the central nervous system ( CNS ) raised concerns, but whether causes neurotoxicity remains unclear. In this study, we demonstrated impairs tight junction endothelial cells increases permeability monocyte transmigration across monolayer in vitro , indicating disrupt blood–brain barrier integrity gain access . primary neuronal cultures resulted decrease cell viability loss antigens. Furthermore, supernatants collected from ‐treated macrophages microglia were also neurotoxic. These significantly increased extracellular levels glutamate following exposure, which negatively correlated viability. Pre‐treatment NMDA receptor antagonist MK 801 alleviated neuron loss, suggesting mediated by glutamate. To determine potential source excess production, investigated glutaminase, main enzyme for generation. Glutaminase was reduced vesicles, induces glutaminase release through vesicles. conclusion, these findings indicate as neurotoxic factor, crucial understanding pollution on image We propose cascade events ‐induced neurotoxicity: inhalable circulation. Circulating cells, disrupts integrity, gains system. injury directly or elevated production The discovery supports an effect