Experimental respiratory exposure to putative Gulf War toxins promotes persistent alveolar macrophage recruitment and pulmonary inflammation.
Experimental respiratory exposure to putative Gulf War toxins promotes persistent alveolar macrophage recruitment and pulmonary inflammation.
复制标题
实验性呼吸道暴露于假定的海湾战争毒素会促进肺泡巨噬细胞持续招募和肺部炎症。
DOI：
10.1016/j.lfs.2021.119839
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发表时间：
2021
期刊：
影响因子：
6.1
通讯作者：
Soloff,AdamC
中科院分区：
文献类型：
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作者：
Powers,AmyA;Jones,KatherineE;Eisenberg,SethH;Rigatti,LoraH;Ryan,JohnP;Luketich,JamesD;Lotze,MichaelT;LaRue,AmandaC;Dhupar,Rajeev;Soloff,AdamC
目的呼吸系统疾病是海湾战争疾病的一个重要组成部分。虽然海湾战争疾病的许多潜在机制仍不明确，但慢性免疫功能障碍是这种多症状，多器官疾病的一贯特征。肺泡巨噬细胞代表肺粘膜的主要单核吞噬细胞，协调宿主对病原体和环境刺激的反应。在此，我们试图表征肺粘膜的先天免疫应答，重点是巨噬细胞，对实验性呼吸道暴露于两种假定的海湾战争毒素（GWT）。我们评估了吸入杀虫剂马拉硫磷和柴油机尾气颗粒物（DEP）对FVB/FVB小鼠肺免疫组成和炎症反应的影响。N小鼠使用多参数光谱细胞仪，细胞因子分析，和histologics.Key findingsAerosolized GWT诱导的总体肺病理与短暂的招聘中性粒细胞和持续积累的肺泡巨噬细胞的肺暴露停止后长达两周。高维细胞计数和无偏计算分析鉴定了由外周单核细胞衍生祖细胞流入驱动的暴露后招募到肺的新的髓样细胞亚群。DEP和马拉硫磷，无论是单独使用还是联合使用，都能诱导支气管肺泡灌洗液中可溶性介质，指示氧化应激（PGF 2 α）、炎症（LTB 4、TNFα、IL-12）和免疫抑制（IL-10），这些发现表明，在没有毒素暴露的情况下，由GWT诱导的巨噬细胞积聚和肺部炎症仍在继续，有助于呼吸道海湾战争疾病的免疫病理学。
AimsRespiratory disorders are a prominent component of Gulf War Illness. Although much of the underlying mechanisms of Gulf War Illness remain undefined, chronic immune dysfunction is a consistent feature of this multi-symptomatic, multi-organ disorder. Alveolar macrophages represent the predominant mononuclear phagocytes of the pulmonary mucosa, orchestrating the host response to pathogens and environmental stimuli. Herein, we sought to characterize the innate immune response of the pulmonary mucosa, with a focus on macrophages, to experimental respiratory exposure to two putative Gulf War Toxins (GWTs).Materials and methodsUtilizing commercially available instrumentation, we evaluated the effect of aerosolized exposure to the pesticide malathion and diesel exhaust particulate (DEP) on the immune composition and inflammatory response of the lung in FVB/N mice using multiparametric spectral cytometry, cytokine analysis, and histology.Key findingsAerosolized GWTs induced gross pulmonary pathology with transient recruitment of neutrophils and sustained accumulation of alveolar macrophages to the lung for up to two weeks after exposure cessation. High-dimensional cytometry and unbiased computational analysis identified novel myeloid subsets recruited to the lung post-exposure driven by an influx of peripheral monocyte-derived progenitors. DEP and malathion, either alone or in combination, induced soluble mediators in bronchoalveolar lavage indicative of oxidative stress (PGF2α), inflammation (LTB4, TNFα, IL-12), and immunosuppression (IL-10), that were sustained or increased two weeks after exposures concluded.SignificanceThese findings indicate that macrophage accumulation and pulmonary inflammation induced by GWTs continue in the absence of toxin exposure and may contribute to the immunopathology of respiratory Gulf War Illness.