National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.
Inhal Toxicol. 2020 May;32(6):265-277. doi: 10.1080/08958378.2020.1781986. Epub 2020 Jun 22.
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. Fine (<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. 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. 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.
来自家畜养殖场的生物颗粒物(BioPM)吸入暴露可能会引发过敏和哮喘患者的病情恶化。本研究旨在使用过敏性哮喘的小鼠模型来确定来自山羊养殖场的 BioPM 对气道过敏反应的影响。从室内山羊养殖场收集细颗粒物(<2.5μm)BioPM。雌性 BALB/c 小鼠经卵清蛋白(OVA)致敏并接受 OVA 或盐水(对照)激发。OVA 和盐水组分为亚组,并分别用不同浓度(0、0.9、3 或 9μg)的山羊养殖场 BioPM 经鼻内暴露。收集支气管肺泡灌洗液(BALF)、血液和肺组织。在盐水激发的小鼠中,山羊养殖场 BioPM 诱导 1)BALF 中性粒细胞呈剂量依赖性增加,2)产生巨噬细胞炎症蛋白-3a。在 OVA 激发的小鼠中,BioPM 诱导 1)BALF 中的炎症细胞,2)OVA 特异性免疫球蛋白(Ig)G1,3)气道粘液分泌特异性基因表达。肺部的 RNAseq 分析表明,中性粒细胞趋化和氧化还原过程分别是盐水和 OVA 激发的小鼠中代表性的基因组途径。单次暴露于山羊养殖场 BioPM 增强了盐水和 OVA 激发的过敏性小鼠的气道炎症,中性粒细胞反应作为 Th17 紊乱,嗜酸性粒细胞反应作为 Th2 紊乱,提示过敏反应的严重程度。鉴定农场 PM 与气道过敏途径相互作用的作用模式将有助于设计潜在的治疗方法。