Belfield-Simpson Lanazha, Martin Jessica R, McPeek Matthew K, Livraghi-Butrico Alessandra, Dang Hong, Kim Yong Ho, Gilmour M Ian, Doerschuk Claire M
Marsico Lung Institute, University of North Carolina, 125 Mason Farm Rd, Chapel Hill, NC, 27599-7246, USA.
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA.
Part Fibre Toxicol. 2025 Jul 29;22(1):21. doi: 10.1186/s12989-025-00625-w.
Burn pits, a method for disposal of military waste outside the United States, produce toxic substances, to which 3.5 million military personnel have been and continue to be exposed. Mild asthma (persistent or intermittent symptoms of asthma but no change in pulmonary function tests) is found among military personnel. We investigated whether burn pit combustion products (CPs) are more detrimental to the airways of asthmatic than non-asthmatic mice.
Mice were exposed to house dust mite antigen (HDM) or phosphate-buffered saline (PBS) 5 times over 2 weeks to initiate asthma-like airway injury. Condensates of CPs or saline were generated by flaming combustion of military cardboard, plastic and military plywood. CPs were aspirated oropharyngeally at 24 h after the final HDM or PBS instillation. The lungs were studied 24 h later.
HDM increased recruitment of eosinophils and mucus projection, both Muc5ac and Muc5b mRNAs and protein. Following exposure to CPs, mice exposed to HDM had a greater inflammatory response and injury, as measured by increased neutrophil recruitment and the concentration of protein in the bronchoalveolar lavage (BAL), than control mice exposed to PBS. Expression of neutrophil chemokines was enhanced. CPs had no effect on HDM-induced eosinophil recruitment or expression of Th2 cytokines. CPs had no effect on mucus production in PBS or HDM mice. However, CPs increased intraluminal mucus, as revealed by AB-PAS staining, only in HDM mice, suggesting that CPs impaired mucociliary clearance (MCC), the lung's primary defense system, only in asthmatic airways. Lung RNA sequencing revealed that CPs increased genes and gene pathways describing inflammatory processes and impaired structure and function of cilia to a greater degree in HDM mice.
These data indicate that asthmatic mice are more susceptible to CP-induced lung remodeling and dysfunction than non-asthmatic mice. Enhanced chemokine expression suggests that the CXCL1,2,5/CXCR2 axis may be the mechanism of the increased neutrophil recruitment. A potential mechanism of mucus accumulation is that inhalation of CPs amplifies the changes in cilia and MCC caused by asthma and triggers a positive feedback loop of enhanced inflammation induced by this accumulating mucus.
燃烧坑是美国境外处理军事垃圾的一种方式，会产生有毒物质，350万军事人员已经并仍在接触这些物质。在军事人员中发现了轻度哮喘（哮喘的持续或间歇性症状，但肺功能测试无变化）。我们调查了燃烧坑燃烧产物（CPs）对哮喘小鼠气道的损害是否比对非哮喘小鼠更严重。
在2周内对小鼠进行5次屋尘螨抗原（HDM）或磷酸盐缓冲盐水（PBS）暴露，以引发类似哮喘的气道损伤。通过燃烧军事纸板、塑料和军事胶合板产生CPs或盐水的冷凝物。在最后一次HDM或PBS滴注后24小时经口咽部吸入CPs。24小时后对肺进行研究。
HDM增加了嗜酸性粒细胞的募集和黏液分泌，包括Muc5ac和Muc5b的mRNA及蛋白。暴露于CPs后，与暴露于PBS的对照小鼠相比，暴露于HDM的小鼠炎症反应和损伤更大，表现为中性粒细胞募集增加和支气管肺泡灌洗（BAL）中蛋白浓度升高。中性粒细胞趋化因子的表达增强。CPs对HDM诱导的嗜酸性粒细胞募集或Th2细胞因子的表达没有影响。CPs对PBS或HDM小鼠的黏液产生没有影响。然而，AB-PAS染色显示，CPs仅在HDM小鼠中增加了管腔内黏液，这表明CPs仅在哮喘气道中损害了黏液纤毛清除（MCC），即肺的主要防御系统。肺RNA测序显示，CPs在HDM小鼠中增加了描述炎症过程的基因和基因通路，并在更大程度上损害了纤毛的结构和功能。
这些数据表明，哮喘小鼠比非哮喘小鼠更容易受到CPs诱导的肺重塑和功能障碍的影响。趋化因子表达增强表明，CXCL1、2、5/CXCR2轴可能是中性粒细胞募集增加的机制。黏液积聚的一个潜在机制是，吸入CPs会放大哮喘引起的纤毛和MCC变化，并触发由这种积聚黏液诱导的炎症增强的正反馈循环。
