Lung Inflammatory Response to Environmental Dust Exposure in Mice Suggests a Link to Regional Respiratory Disease Risk.
Lung Inflammatory Response to Environmental Dust Exposure in Mice Suggests a Link to Regional Respiratory Disease Risk.
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DOI：
10.2147/jir.s320096
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发表时间：
2021
影响因子：
4.5
通讯作者：
Nordgren TM
中科院分区：
文献类型：
--
作者：
Burr AC;Velazquez JV;Ulu A;Kamath R;Kim SY;Bilg AK;Najera A;Sultan I;Botthoff JK;Aronson E;Nair MG;Nordgren TM
加利福尼亚州最大的湖泊索尔顿海被指定为农业排水水库。近年来，由于水源减少、周边地区气溶胶粉尘含量增加，该湖面积不断缩小。与加州其他地区相比，索尔顿海周边社区的哮喘患病率有所增加；然而，粉尘吸入与肺部健康影响之间的联系尚未确定。我们使用已建立的鼻内粉尘暴露小鼠模型来研究单次或重复（7 天）接触索尔顿海周边地区收集的粉尘提取物 (SSDE) 后的肺部炎症反应，并辅以评估 SSDE 对气道上皮影响的体外研究。在这些研究中，单次或重复 SSDE 暴露诱导显着的肺部炎症细胞因子释放并伴随中性粒细胞流入。重复的 SSDE 暴露导致肺部嗜酸性粒细胞显着募集，并改变与过敏原介导的免疫反应相关的基因（包括 Clec4e）的表达。 SSDE 处理人支气管上皮细胞 (BEAS-2B) 在处理后 5 小时和 24 小时诱导炎症细胞因子的产生。当 BEAS-2B 暴露于蛋白酶活性耗尽的 SSDE (PDSSDE) 或在蛋白酶激活受体 1 和 -2 拮抗作用下用 SSDE 处理时，炎症细胞因子的释放减少。此外，与 SSDE 攻击的小鼠相比，重复暴露于 PDSSDE 导致小鼠中性粒细胞和嗜酸性粒细胞流入以及 IL-6 释放减少。这些研究表明，SSDE 产生了强烈的肺部炎症反应和组织重塑，部分原因是粉尘中发现的环境蛋白酶。这些研究提供了第一个证据，支持索尔顿海地区环境灰尘暴露、蛋白酶介导的免疫激活和呼吸道疾病之间的联系。
The Salton Sea, California’s largest lake, is designated as an agricultural drainage reservoir. In recent years, the lake has experienced shrinkage due to reduced water sources, increasing levels of aerosolized dusts in surrounding regions. Communities surrounding the Salton Sea have increased asthma prevalence versus the rest of California; however, a connection between dust inhalation and lung health impacts has not been defined. We used an established intranasal dust exposure murine model to study the lung inflammatory response following single or repetitive (7-day) exposure to extracts of dusts collected in regions surrounding the Salton Sea (SSDE), complemented with in vitro investigations assessing SSDE impacts on the airway epithelium. In these investigations, single or repetitive SSDE exposure induced significant lung inflammatory cytokine release concomitant with neutrophil influx. Repetitive SSDE exposure led to significant lung eosinophil recruitment and altered expression of genes associated with allergen-mediated immune response, including Clec4e. SSDE treatment of human bronchial epithelial cells (BEAS-2B) induced inflammatory cytokine production at 5- and 24-hours post-treatment. When BEAS-2B were exposed to protease activity-depleted SSDE (PDSSDE) or treated with SSDE in the context of protease-activated receptor-1 and −2 antagonism, inflammatory cytokine release was decreased. Furthermore, repetitive exposure to PDSSDE led to decreased neutrophil and eosinophilic influx and IL-6 release in mice compared to SSDE-challenged mice. These investigations demonstrate potent lung inflammatory responses and tissue remodeling in response to SSDE, in part due to environmental proteases found within the dusts. These studies provide the first evidence supporting a link between environmental dust exposure, protease-mediated immune activation, and respiratory disease in the Salton Sea region.