Differential pulmonary toxicity and autoantibody formation in genetically distinct mouse strains following combined exposure to silica and diesel exhaust particles.

IF 7.2 1区 医学 Q1 TOXICOLOGY
Lisa Mf Janssen, Frauke Lemaire, Nora Fopke Marain, Steven Ronsmans, Natasja Heylen, Arno Vanstapel, Greetje Vande Velde, Jeroen Aj Vanoirbeek, Kenneth Michael Pollard, Manosij Ghosh, Peter Hm Hoet
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引用次数: 0

Abstract

Background: 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.

Results: 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.

Conclusion: 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.

基因不同的小鼠品系在联合接触二氧化硅和柴油机废气颗粒后肺部毒性和自身抗体形成的差异。
背景:吸入空气中的微粒物质(如二氧化硅和柴油机废气微粒)会对呼吸系统和全身健康造成严重的长期危害。接触二氧化硅可导致矽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。采矿业中常见的二氧化硅和二乙基乙基化合物的联合暴露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二乙基乙基吡咯烷酮对两个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联合影响,从而了解遗传易感性、微粒暴露和疾病结果之间的相互作用。小鼠经口咽吸入二氧化硅和柴油机废气颗粒。对肺损伤和宿主反应的评估包括体内肺部微型计算机断层扫描、肺功能测试、支气管肺泡灌洗液分析(包括炎症细胞因子和抗核抗体)以及颗粒共聚焦组织病理学:结果:研究结果表明,二氧化硅和柴油机废气颗粒(DEP)对 C57BL/6J 和 NOD/ShiLtJ 小鼠的肺损伤、炎症和自身抗体形成有不同的影响。暴露于二氧化硅会引起成熟的炎症反应,表现为炎症浸润、细胞因子和趋化因子的释放,以及轻度纤维化,表现为 C57BL/6J 和 NOD/ShilLtJ 小鼠肺部的胶原沉积。值得注意的是,这些品系在呼吸功能和肺容量方面表现出不同的反应,这是由微型计算机断层扫描评估得出的结果。此外,二氧化硅暴露会诱发气道高反应性和支气管肺泡灌洗液中抗核抗体水平的升高,这在 NOD/ShiLtJ 小鼠中尤为突出。此外,抗核抗体与 NOD/ShiLTJ 小鼠肺部炎症的程度相关。肺组织分析显示了含有 DEP 的巨噬细胞以及二氧化硅和 DEP 颗粒的共定位。然而,除了导致 NOD/ShiLtJ 小鼠气道过度反应外,环境水平的 DEP 并没有显著放大二氧化硅诱导的效应。没有证据表明这些特定剂量的二氧化硅和 DEP 在诱发小鼠肺损伤或炎症方面存在协同或叠加作用:结论:小鼠品系的变化对二氧化硅诱导的肺部病变的发展有很大影响。此外,环境水平的 DEP 对这些二氧化硅诱导效应的额外影响微乎其微。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
15.90
自引率
4.00%
发文量
69
审稿时长
6 months
期刊介绍: Particle and Fibre Toxicology is an online journal that is open access and peer-reviewed. It covers a range of disciplines such as material science, biomaterials, and nanomedicine, focusing on the toxicological effects of particles and fibres. The journal serves as a platform for scientific debate and communication among toxicologists and scientists from different fields who work with particle and fibre materials. The main objective of the journal is to deepen our understanding of the physico-chemical properties of particles, their potential for human exposure, and the resulting biological effects. It also addresses regulatory issues related to particle exposure in workplaces and the general environment. Moreover, the journal recognizes that there are various situations where particles can pose a toxicological threat, such as the use of old materials in new applications or the introduction of new materials altogether. By encompassing all these disciplines, Particle and Fibre Toxicology provides a comprehensive source for research in this field.
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