Airborne particulate matter from goat farm increases acute allergic airway responses in mice

<b>Background:</b> Inhalation exposure to biological particulate matter (BioPM) from livestock farms may provoke exacerbations in subjects suffering from allergy and asthma. The aim of this study was to use a murine model of allergic asthma to determine the effect of BioPM derived from goat farm on airway allergic responses. <b>Methods:</b> Fine (&lt;2.5 μm) BioPM was collected from an indoor goat stable. Female BALB/c mice were ovalbumin (OVA) sensitized and challenged with OVA or saline as control. The OVA and saline groups were divided in sub-groups and exposed intranasally to different concentrations (0, 0.9, 3, or 9 μg) of goat farm BioPM. Bronchoalveolar lavage fluid (BALF), blood and lung tissues were collected. <b>Results:</b> In saline-challenged mice, goat farm BioPM induced 1) a dose-dependent increase in neutrophils in BALF and 2) production of macrophage inflammatory protein-3a. In OVA-challenged mice, BioPM induced 1) inflammatory cells in BALF, 2) OVA-specific Immunoglobulin (Ig)G1, 3) airway mucus secretion-specific gene expression. RNAseq analysis of lungs indicates that neutrophil chemotaxis and oxidation-reduction processes were the representative genomic pathways in saline and OVA-challenged mice, respectively. <b>Conclusions:</b> A single exposure to goat farm BioPM enhanced airway inflammation in both saline and OVA-challenged allergic mice, with neutrophilic response as Th17 disorder and eosinophilic response as Th2 disorder indicative of the severity of allergic responses. Identification of the mode of action by which farm PM interacts with airway allergic pathways will be useful to design potential therapeutic approaches.

<b>研究背景：</b> 畜牧场来源的生物颗粒物（biological particulate matter, BioPM）经呼吸道暴露，可诱发过敏及哮喘患者的病情急性加重。本研究旨在利用过敏性哮喘小鼠模型，探究山羊场来源的生物颗粒物对气道过敏反应的影响。<b>研究方法：</b> 从室内山羊舍采集细粒径（<2.5 μm）生物颗粒物。对雌性BALB/c小鼠以卵清蛋白（ovalbumin, OVA）进行致敏，并分别以OVA或生理盐水（saline）进行激发，其中生理盐水组作为对照。随后将OVA激发组与生理盐水激发组进一步分为亚组，经鼻内暴露于不同浓度（0、0.9、3或9 μg）的山羊场生物颗粒物。收集支气管肺泡灌洗液（bronchoalveolar lavage fluid, BALF）、血液及肺组织样本。<b>研究结果：</b> 在生理盐水激发的小鼠中，山羊场生物颗粒物可诱导：1）支气管肺泡灌洗液中中性粒细胞呈剂量依赖性升高；2）巨噬细胞炎症蛋白-3α的产生。在OVA激发的小鼠中，生物颗粒物可诱导：1）支气管肺泡灌洗液中炎症细胞浸润；2）OVA特异性免疫球蛋白G1（immunoglobulin G1, IgG1）的生成；3）气道黏液分泌相关基因的表达。肺组织RNA测序（RNAseq）分析显示，在生理盐水激发组与OVA激发组小鼠中，分别以中性粒细胞趋化与氧化还原过程为代表性基因组通路。<b>研究结论：</b> 单次暴露于山羊场生物颗粒物，可加重生理盐水激发与OVA激发的过敏性小鼠的气道炎症，其中中性粒细胞性反应对应Th17紊乱、嗜酸性粒细胞性反应对应Th2紊乱，二者可作为过敏反应严重程度的指示指标。阐明畜牧场颗粒物与气道过敏通路的相互作用机制，可为潜在治疗策略的设计提供依据。