ABSTRACT

The Southwestern United States has a legacy of industrial mining due to the presence of rich mineral ore deposits. The relationship between environmental inhaled particulate matter (PM) exposures and neurological outcomes within an autoimmune context is understudied. The aim of this study was to compare two regionally-relevant dusts from high-priority abandoned mine-sites, Claim 28 PM, from Blue Gap Tachee, AZ and St. Anthony mine PM, from the Pueblo of Laguna, NM and to expose autoimmune-prone mice (NZBWF1/J). Mice were randomly assigned to one of three groups (n = 8/group): DM (dispersion media, control), Claim 28 PM, or St. Anthony PM, subjected to oropharyngeal aspiration of (100 µg/50 µl), once per week for a total of 4 consecutive doses. A battery of immunological and neurological endpoints was assessed at 24 weeks of age including: bronchoalveolar lavage cell counts, lung gene expression, brain immunohistochemistry, behavioral tasks and serum autoimmune biomarkers. Bronchoalveolar lavage results demonstrated a significant increase in number of polymorphonuclear neutrophils following Claim 28 and St. Anthony mine PM aspiration. Lung mRNA expression showed significant upregulation in CCL-2 and IL-1ß following St. Anthony mine PM aspiration. In addition, neuroinflammation was present in both Claim 28 and St. Anthony mine-site derived PM exposure groups. Behavioral tasks resulted in significant deficits as determined by Y-maze new arm frequency following Claim 28 aspiration. Neutrophil elastase was significantly upregulated in the St. Anthony mine exposure group. Interestingly, there were no significant changes in serum autoantigens suggesting systemic inflammatory effects may be mediated through other molecular mechanisms following low-dose PM exposures.

 抽象的

由于存在丰富的矿藏，美国西南部拥有工业采矿的传统。在自身免疫背景下，环境吸入颗粒物 (PM) 暴露与神经系统结果之间的关系尚未得到充分研究。本研究的目的是比较来自高度优先废弃矿场（亚利桑那州 Blue Gap Tachee 的下午 28 号）和新墨西哥州拉古纳普韦布洛的圣安东尼矿 PM 的两种区域相关粉尘，并揭示自身免疫性-倾向小鼠（NZBWF1/J）。将小鼠随机分配到三组之一（n = 8/组）：DM（分散介质，对照）、Claim 28 PM 或 St. Anthony PM，接受口咽抽吸（100 µg/50 µl），每组一次一周共连续 4 剂。在 24 周龄时评估了一系列免疫学和神经学终点，包括：支气管肺泡灌洗细胞计数、肺基因表达、脑免疫组织化学、行为任务和血清自身免疫生物标志物。支气管肺泡灌洗结果表明，在权利要求 28 和圣安东尼矿 PM 抽吸后，多形核中性粒细胞的数量显着增加。圣安东尼矿 PM 吸入后，肺 mRNA 表达显示 CCL-2 和 IL-1ß 显着上调。此外，在权利要求 28 和圣安东尼矿场衍生的 PM 暴露组中都存在神经炎症。根据权利要求 28 愿望后 Y 迷宫新臂频率确定，行为任务导致显着缺陷。圣安东尼地雷暴露组的中性粒细胞弹性蛋白酶显着上调。有趣的是，血清自身抗原没有显着变化，表明低剂量 PM 暴露后可能通过其他分子机制介导全身炎症反应。