Pacheco Yves, Ponchon Marine, Lebecque Serge, Calender Alain, Bernaudin Jean François, Valeyre Dominique, Iglarz Marc, Strasser Daniel S, Studer Rolf, Freti Diego, Renno Toufiq, Bentaher Abederrazzaq
a Inflammation and Immunity of the Respiratory Epithelium 1 - EA7426, Faculté de médecine Lyon Sud , UCBL1, Pierre Benite , France.
b Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon2 , Pierre Benite , France.
Exp Lung Res. 2018 Feb;44(1):25-39. doi: 10.1080/01902148.2017.1412541. Epub 2018 Jan 11.
Nanoparticles are increasingly suspected as a strong etiologic factor of granuloma formation.
The aim of our study was to compare lung inflammatory response and histology changes following exposure of mice to two widely used nanoparticles: carbon nanotubes (MWCNT) and cadmium-based nanoparticles (QDOT705) in an attempt to better our understanding of granulomatous inflammation.
Various groups of mice were included: control mice and mice that were intranasally instilled with QDOT or MWCNT. At defined time points post-challenge, bronchoalveolar lavages (BALs) and lung tissues were collected to study inflammatory and histologic changes.
Analyses of lung BAL fluids and tissues of nanoparticles-challenged mice in comparison to controls found: (1) increased cellularity in BALs, (2) increase of total protein concentration, LDH activity and proteolytic activity in BALs; (3) patchy granulomas, (4) macrophages, CD3 ± T, Treg and B cell infiltration in granulomatous areas; and (5) altered regulation of key inflammatory mediators and receptors. Importantly, these changes were nanoparticle type-dependent.
Our work enhances understanding of nanoparticles-induced lung inflammatory and histological changes that result in granuloma formation. We provide compelling evidence that not only exposure to nanoparticles leads to granulomatous lung inflammation, but the severity of this latter is nanostructure type-dependent. Of importance, while nanotechnology has the potential to revolutionize various fields including medicine, nanoparticles form the potential for an entirely new lung health risk that it is necessary to take seriously into consideration by setting up and/or reinforcing adequate safety measures.
纳米颗粒越来越被怀疑是肉芽肿形成的一个重要病因。
我们研究的目的是比较小鼠暴露于两种广泛使用的纳米颗粒(碳纳米管(MWCNT)和镉基纳米颗粒(QDOT705))后肺部的炎症反应和组织学变化,以更好地理解肉芽肿性炎症。
纳入多组小鼠:对照组小鼠以及经鼻滴注QDOT或MWCNT的小鼠。在攻击后的特定时间点,收集支气管肺泡灌洗液(BAL)和肺组织,以研究炎症和组织学变化。
与对照组相比,对纳米颗粒攻击小鼠的肺BAL液和组织进行分析发现:(1)BAL中的细胞数量增加;(2)BAL中总蛋白浓度、乳酸脱氢酶活性和蛋白水解活性增加;(3)散在性肉芽肿;(4)肉芽肿区域有巨噬细胞、CD3±T细胞、调节性T细胞和B细胞浸润;(5)关键炎症介质和受体的调节改变。重要的是,这些变化依赖于纳米颗粒的类型。
我们的工作增进了对纳米颗粒诱导的导致肉芽肿形成的肺部炎症和组织学变化的理解。我们提供了令人信服的证据,不仅纳米颗粒暴露会导致肉芽肿性肺部炎症,而且后者的严重程度取决于纳米结构的类型。重要的是,虽然纳米技术有潜力变革包括医学在内的各个领域,但纳米颗粒构成了一种全新的肺部健康风险,有必要通过建立和/或加强适当的安全措施来认真加以考虑。