Qiu Xia-Wen, Zhang Wenting, Chen Xuefei, Luo Guofu, Qi Xiaoyan, Guo Qiaoqi, Zhou Xinyan, Sun Xinhai, Xiang Hai, Feng Huajun, Wen Xuehuan, Bai Songjie
Jinhua Academy of Zhejiang Chinese Medical University, Jinhua, Zhejiang 321015, China; Zhejiang Key Laboratory of Ecological Environmental Damage Control and Value Transformation, College of Environment and Resources, College of Carbon Neutral, Zhejiang A & F University, Hangzhou, Zhejiang 311300, China.
Department of Infectious Diseases, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
J Hazard Mater. 2025 Sep 15;496:139277. doi: 10.1016/j.jhazmat.2025.139277. Epub 2025 Jul 16.
N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-Q) has garnered considerable attention due to its deadly biological toxicity. However, the effects of 6PPD-Q exposure on mammalian respiratory function remain uncertain. This study developed a murine model using 14-day consecutive intranasal administration of environmentally relevant 6PPD-Q doses, followed by intratracheal Klebsiella pneumoniae (KP) injection, to evaluate the biological effects of 6PPD-Q respiratory exposure on pulmonary innate immunity. Our findings revealed that 6PPD-Q respiratory exposure induced significant damage to lung but not to extrapulmonary organs. Notably, mice respiratorily exposed to 6PPD-Q exhibited with more severe intrapulmonary inflammation, higher bacterial load, and poorer survival rates when challenged with KP pneumonia. These phenomena may be attributed to the increase in CD11cCD11b alveolar macrophages (AMs) in the lungs, which exhibit impaired innate immune functions and attenuated chemotactic responsiveness. Transcriptome analysis further demonstrated downregulated expression of chemokine genes Ccl2, Cxcl1, and Cxcl2 in CD11cCD11b AMs. Overall, our findings reveal that 6PPD-Q respiratory exposure aggravates bacterial pneumonia by impairing the innate immune functions of AMs. These findings enhance our understanding of 6PPD-Q health risks and provide a scientific foundation for developing effective treatments for 6PPD-Q-induced respiratory disorders.
N-（1,3-二甲基丁基）-N'-苯基-对苯二胺醌（6PPD-Q）因其致命的生物毒性而备受关注。然而，6PPD-Q暴露对哺乳动物呼吸功能的影响仍不确定。本研究建立了一种小鼠模型，连续14天经鼻给予与环境相关剂量的6PPD-Q，随后气管内注射肺炎克雷伯菌（KP），以评估6PPD-Q经呼吸道暴露对肺部固有免疫的生物学效应。我们的研究结果表明，6PPD-Q经呼吸道暴露会对肺部造成显著损伤，但对肺外器官无影响。值得注意的是，经呼吸道暴露于6PPD-Q的小鼠在感染KP肺炎时表现出更严重的肺内炎症、更高的细菌载量和更低的存活率。这些现象可能归因于肺内CD11cCD11b肺泡巨噬细胞（AMs）数量增加，这些细胞表现出固有免疫功能受损和趋化反应减弱。转录组分析进一步表明，CD11cCD11b AMs中趋化因子基因Ccl2、Cxcl1和Cxcl2的表达下调。总体而言，我们的研究结果表明，6PPD-Q经呼吸道暴露会通过损害AMs的固有免疫功能而加重细菌性肺炎。这些发现加深了我们对6PPD-Q健康风险的理解，并为开发针对6PPD-Q诱导的呼吸系统疾病的有效治疗方法提供了科学依据。
