A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA, USA.
Part Fibre Toxicol. 2024 Feb 15;21(1):6. doi: 10.1186/s12989-024-00564-y.
Air pollution is recognized as an emerging environmental risk factor for neurological diseases. Large-scale epidemiological studies associate traffic-related particulate matter (PM) with impaired cognitive functions and increased incidence of neurodegenerative diseases such as Alzheimer's disease. Inhaled components of PM may directly invade the brain via the olfactory route, or act through peripheral system responses resulting in inflammation and oxidative stress in the brain. Microglia are the immune cells of the brain implicated in the progression of neurodegenerative diseases. However, it remains unknown how PM affects live human microglia.
Here we show that two different PMs derived from exhausts of cars running on EN590 diesel or compressed natural gas (CNG) alter the function of human microglia-like cells in vitro. We exposed human induced pluripotent stem cell (iPSC)-derived microglia-like cells (iMGLs) to traffic related PMs and explored their functional responses. Lower concentrations of PMs ranging between 10 and 100 µg ml increased microglial survival whereas higher concentrations became toxic over time. Both tested pollutants impaired microglial phagocytosis and increased secretion of a few proinflammatory cytokines with distinct patterns, compared to lipopolysaccharide induced responses. iMGLs showed pollutant dependent responses to production of reactive oxygen species (ROS) with CNG inducing and EN590 reducing ROS production.
Our study indicates that traffic-related air pollutants alter the function of human microglia and warrant further studies to determine whether these changes contribute to adverse effects in the brain and on cognition over time. This study demonstrates human iPSC-microglia as a valuable tool to study functional microglial responses to environmental agents.
空气污染被认为是神经退行性疾病的新兴环境风险因素。大规模的流行病学研究表明，交通相关的颗粒物（PM）与认知功能受损以及阿尔茨海默病等神经退行性疾病的发病率增加有关。PM 的吸入成分可能通过嗅觉途径直接侵入大脑，或者通过外周系统反应作用，导致大脑中的炎症和氧化应激。小胶质细胞是大脑中的免疫细胞，与神经退行性疾病的进展有关。然而，PM 如何影响活体人类小胶质细胞尚不清楚。
在这里，我们展示了两种不同的源自汽车尾气的 PM，分别来自使用 EN590 柴油或压缩天然气（CNG）的汽车，这两种 PM 改变了体外人类小胶质细胞样细胞的功能。我们将人类诱导多能干细胞（iPSC）衍生的小胶质细胞样细胞（iMGL）暴露于交通相关的 PM 中，并探索了它们的功能反应。较低浓度的 PM（10 到 100μg/ml）增加了小胶质细胞的存活率，而较高浓度的 PM 随着时间的推移变得有毒。与脂多糖诱导的反应相比，两种测试的污染物都损害了小胶质细胞的吞噬作用，并增加了少数促炎细胞因子的分泌，且具有不同的模式。iMGL 对活性氧（ROS）的产生表现出依赖于污染物的反应，其中 CNG 诱导 ROS 产生，而 EN590 则减少 ROS 产生。
我们的研究表明，交通相关的空气污染物改变了人类小胶质细胞的功能，需要进一步研究以确定这些变化是否会导致大脑和认知功能随着时间的推移而产生不良影响。本研究表明，人类 iPSC-小胶质细胞是研究环境因子对功能小胶质细胞反应的一种有价值的工具。
