Burr Abigail C, Velazquez Jalene V, Ulu Arzu, Kamath Rohan, Kim Sang Yong, Bilg Amanpreet K, Najera Aileen, Sultan Iman, Botthoff Jon K, Aronson Emma, Nair Meera G, Nordgren Tara M
Division of Biomedical Sciences, University of California Riverside, Riverside, CA, 92521, USA.
Center for Conservation Biology, University of California Riverside, Riverside, CA, 92521, USA.
J Inflamm Res. 2021 Aug 21;14:4035-4052. doi: 10.2147/JIR.S320096. eCollection 2021.
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.
加利福尼亚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，该湖泊面积不断缩小，周边地区空气中的粉尘含量增加。与加利福尼亚其他地区相比，索尔顿海周边社区的哮喘患病率有所上升；然而，吸入粉尘与肺部健康影响之间的联系尚未明确。
我们使用已建立的鼻内粉尘暴露小鼠模型，研究单次或重复（7天）暴露于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，并辅以体外研究，评估SSDE对气道上皮的影响。
在这些研究中，单次或重复暴露于SSDE会诱导显著的肺部炎症细胞因子释放，并伴有中性粒细胞流入。重复暴露于SSDE会导致显著的肺部嗜酸性粒细胞募集，并改变与变应原介导的免疫反应相关的基因表达，包括Clec4e。用SSDE处理人支气管上皮细胞（BEAS-2B）后5小时和24小时会诱导炎症细胞因子产生。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拮抗的情况下用SSDE处理时，炎症细胞因子释放减少。此外，与接受SSDE攻击的小鼠相比，重复暴露于PDSSDE会导致小鼠中性粒细胞和嗜酸性粒细胞流入减少以及IL-6释放减少。
这些研究表明，SSDE会引发强烈的肺部炎症反应和组织重塑，部分原因是粉尘中存在环境蛋白酶。这些研究提供了首个证据，支持索尔顿海地区环境粉尘暴露、蛋白酶介导的免疫激活与呼吸系统疾病之间存在联系。
