Inhalation of airborne particulate matter, such as silica and diesel exhaust particles, poses serious long-term respiratory and systemic health risks. Silica exposure can lead to silicosis and systemic autoimmune diseases, while DEP exposure is linked to asthma and cancer. Combined exposure to silica and DEP, common in mining, may have more severe effects. This study investigates the separate and combined effects of occupational-level silica and ambient-level DEP on lung injury, inflammation, and autoantibody formation in two genetically distinct mouse strains, thereby aiming at understanding the interplay between genetic susceptibility, particulate exposure, and disease outcomes. Silica and diesel exhaust particles were administered to mice via oropharyngeal aspiration. Assessments of lung injury and host response included in vivo lung micro-computed tomography, lung function tests, bronchoalveolar lavage fluid analysis including inflammatory cytokines and antinuclear antibodies, and histopathology with particle colocalization. The findings highlight the distinct effects of silica and diesel exhaust particles (DEP) on lung injury, inflammation, and autoantibody formation in C57BL/6J and NOD/ShiLtJ mice. Silica exposure elicited a well-established inflammatory response marked by inflammatory infiltrates, release of cytokines, and chemokines, alongside mild fibrosis, indicated by collagen deposition in the lungs of both C57BL/6J and NOD/ShilLtJ mice. Notably, these strains exhibited divergent responses in terms of respiratory function and lung volumes, as assessed through micro-computed tomography. Additionally, silica exposure induced airway hyperreactivity and elevated antinuclear antibody levels in bronchoalveolar lavage fluid, particularly prominent in NOD/ShiLtJ mice. Moreover, antinuclear antibodies correlated with extent of lung inflammation in NOD/ShiLTJ mice. Lung tissue analysis revealed DEP loaded macrophages and co-localization of silica and DEP particles. However, aside from contributing to airway hyperreactivity specifically in NOD/ShiLtJ mice, the ambient-level DEP did not significantly amplify the effects induced by silica. There was no evidence of synergistic or additive interaction between these specific doses of silica and DEP in inducing lung damage or inflammation in either of the mouse strains. Mouse strain variations exerted a substantial influence on the development of silica induced lung alterations. Furthermore, the additional impact of ambient-level DEP on these silica-induced effects was minimal.

中文翻译：

---

联合暴露于二氧化硅和柴油机尾气颗粒后，基因不同的小鼠品系的不同肺毒性和自身抗体形成

吸入空气中的颗粒物，例如二氧化硅和柴油机尾气颗粒，会造成严重的长期呼吸道和全身健康风险。接触二氧化硅会导致硅肺病和全身性自身免疫性疾病，而接触 DEP 则与哮喘和癌症有关。在采矿业中，同时接触二氧化硅和 DEP 可能会产生更严重的影响。本研究调查了职业水平的二氧化硅和环境水平的 DEP 对两种基因不同的小鼠品系的肺损伤、炎症和自身抗体形成的单独和综合影响，从而旨在了解遗传易感性、颗粒物暴露和疾病结果之间的相互作用。通过口咽抽吸将二氧化硅和柴油机尾气颗粒给予小鼠。肺损伤和宿主反应的评估包括体内肺微计算机断层扫描、肺功能测试、支气管肺泡灌洗液分析（包括炎性细胞因子和抗核抗体）以及颗粒共定位的组织病理学。研究结果强调了二氧化硅和柴油机尾气颗粒 (DEP) 对 C57BL/6J 和 NOD/ShiLtJ 小鼠肺损伤、炎症和自身抗体形成的独特影响。二氧化硅暴露引发了明显的炎症反应，其特征是炎症浸润、细胞因子和趋化因子的释放，以及轻度纤维化，这由 C57BL/6J 和 NOD/ShilLtJ 小鼠肺部的胶原沉积表明。值得注意的是，通过微型计算机断层扫描评估，这些菌株在呼吸功能和肺容量方面表现出不同的反应。此外，二氧化硅暴露会诱导气道高反应性和支气管肺泡灌洗液中抗核抗体水平升高，这在 NOD/ShiLtJ 小鼠中尤其突出。此外，抗核抗体与 NOD/ShiLTJ 小鼠肺部炎症程度相关。肺组织分析显示巨噬细胞负载 DEP 以及二氧化硅和 DEP 颗粒的共定位。然而，除了导致 NOD/ShiLtJ 小鼠气道高反应性外，环境水平的 DEP 并没有显着放大二氧化硅引起的影响。没有证据表明这些特定剂量的二氧化硅和 DEP 之间在诱导任一小鼠品系的肺损伤或炎症方面存在协同或附加相互作用。小鼠品系变异对二氧化硅诱导的肺部改变的发展产生了重大影响。此外，环境水平 DEP 对这些二氧化硅引起的影响的额外影响很小。