Neuroinflammatory and Neurometabolomic Consequences From Inhaled Wildfire Smoke-Derived Particulate Matter in the Western United States.
Neuroinflammatory and Neurometabolomic Consequences From Inhaled Wildfire Smoke-Derived Particulate Matter in the Western United States.
复制标题
美国西部吸入野火烟雾衍生颗粒物造成的神经炎症和神经代谢后果。
DOI：
10.1093/toxsci/kfab147
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Canal,Christop
中科院分区：
文献类型：
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作者：
Scieszka,David;Hunter,Russell;Begay,Jessica;Bitsui,Marsha;Lin,Yan;Galewsky,Joseph;Morishita,Masako;Klaver,Zachary;Wagner,James;Harkema,JackR;Herbert,Guy;Lucas,Selita;McVeigh,Charlotte;Bolt,Alicia;Bleske,Barry;Canal,Christop
利用距离野火烟雾（WFS）源>300 km的移动的实验室，本研究检查了全身免疫反应特征，重点是2020年在加州，亚利桑那州和华盛顿吸入暴露于自然发生的野火引起的神经炎症和神经代谢组学后果。在位于新墨西哥州的一个移动的实验室中暴露20天（4小时/天）后，吸入WFPM导致明显的神经炎症，而外周免疫活动（肺、骨髓）似乎在C57 BL/6小鼠中得到解决。重要的是，WFPM暴露增加脑血管内皮细胞活化和粘附分子（VCAM-1和ICAM-1）的表达，除了增加神经胶质细胞活化和外周免疫细胞浸润到大脑。流式细胞术分析显示，小胶质细胞和外周免疫亚群在WFPM暴露小鼠的大脑中的促炎表型。有趣的是，内皮细胞神经免疫活性与PECAM-1表达水平差异相关，表明脑血管内皮细胞亚群在暴露20天后过渡到炎症消退。WFPM暴露降低了与抗衰老保护相关的神经代谢物，如NAD+和牛磺酸。此外，观察到病理性淀粉样β蛋白积聚增加，这是神经变性的标志。神经炎症以及关键神经代谢物水平的降低反映了一系列结果，这些结果在引发炎症和衰老相关的神经退行性表型方面具有重要意义。
Utilizing a mobile laboratory located >300 km away from wildfire smoke (WFS) sources, this study examined the systemic immune response profile, with a focus on neuroinflammatory and neurometabolomic consequences, resulting from inhalation exposure to naturally occurring wildfires in California, Arizona, and Washington in 2020. After a 20-day (4 h/day) exposure period in a mobile laboratory stationed in New Mexico, WFS-derived particulate matter (WFPM) inhalation resulted in significant neuroinflammation while immune activity in the peripheral (lung, bone marrow) appeared to be resolved in C57BL/6 mice. Importantly, WFPM exposure increased cerebrovascular endothelial cell activation and expression of adhesion molecules (VCAM-1 and ICAM-1) in addition to increased glial activation and peripheral immune cell infiltration into the brain. Flow cytometry analysis revealed proinflammatory phenotypes of microglia and peripheral immune subsets in the brain of WFPM-exposed mice. Interestingly, endothelial cell neuroimmune activity was differentially associated with levels of PECAM-1 expression, suggesting that subsets of cerebrovascular endothelial cells were transitioning to resolution of inflammation following the 20-day exposure. Neurometabolites related to protection against aging, such as NAD+and taurine, were decreased by WFPM exposure. Additionally, increased pathological amyloid-beta protein accumulation, a hallmark of neurodegeneration, was observed. Neuroinflammation, together with decreased levels of key neurometabolites, reflect a cluster of outcomes with important implications in priming inflammaging and aging-related neurodegenerative phenotypes.