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Macrophage autophagy protects mice from cerium oxide nanoparticle-induced lung fibrosis
Particle and Fibre Toxicology ( IF 10 ) Pub Date : 2021-02-01 , DOI: 10.1186/s12989-021-00398-y
Balasubramanyam Annangi 1 , Zhuyi Lu 1 , Jonathan Bruniaux 1 , Audrey Ridoux 1 , Vanessa Marques da Silva 1 , Delphine Vantelon 2 , Jorge Boczkowski 1, 3 , Sophie Lanone 1
Affiliation  

Cerium (Ce) is a rare earth element, rapidly oxidizing to form CeO2, and currently used in numerous commercial applications, especially as nanoparticles (NP). The potential health effects of Ce remain uncertain, but literature indicates the development of rare earth pneumoconiosis accompanied with granuloma formation, interstitial fibrosis and inflammation. The exact underlying mechanisms are not yet completely understood, and we propose that autophagy could be an interesting target to study, particularly in macrophages. Therefore, the objective of our study was to investigate the role of macrophagic autophagy after pulmonary exposure to CeO2 NP in mice. Mice lacking the early autophagy gene Atg5 in their myeloid lineage and their wildtype counterparts were exposed to CeO2 NP by single oropharyngeal administration and sacrificed up to 1 month after. At that time, lung remodeling was thoroughly characterized (inflammatory cells infiltration, expression of fibrotic markers such as αSMA, TGFβ1, total and type I and III collagen deposition), as well as macrophage infiltration (quantification and M1/M2 phenotype). Such pulmonary exposure to CeO2 NP induces a progressive and dose-dependent lung fibrosis in the bronchiolar and alveolar walls, together with the activation of autophagy. Blockage of macrophagic autophagy protects from alveolar but not bronchiolar fibrosis, via the modulation of macrophage polarization towards M2 phenotype. In conclusion, our findings bring novel insight on the role of macrophagic autophagy in lung fibrogenesis, and add to the current awareness of pulmonary macrophages as important players in the disease.

中文翻译:

巨噬细胞自噬保护小鼠免受氧化铈纳米颗粒诱导的肺纤维化

铈 (Ce) 是一种稀土元素,可快速氧化形成 CeO2,目前用于许多商业应用,尤其是作为纳米颗粒 (NP)。Ce 的潜在健康影响仍然不确定,但文献表明稀土尘肺的发展伴随着肉芽肿形成、间质纤维化和炎症。确切的潜在机制尚未完全了解,我们认为自噬可能是一个有趣的研究目标,尤其是在巨噬细胞中。因此,我们研究的目的是研究小鼠肺部暴露于 CeO2 NP 后巨噬细胞自噬的作用。在骨髓谱系中缺乏早期自噬基因 Atg5 的小鼠及其野生型小鼠通过单次口咽给药暴露于 CeO2 NP 并在长达 1 个月后处死。当时,肺重塑得到彻底表征(炎症细胞浸润、纤维化标志物的表达,如αSMA、TGFβ1、总和 I 型和 III 型胶原沉积),以及巨噬细胞浸润(量化和 M1/M2 表型)。这种肺部暴露于 CeO2 NP 会在细支气管和肺泡壁中诱导进行性和剂量依赖性肺纤维化,同时激活自噬。通过调节巨噬细胞向 M2 表型的极化,巨噬细胞自噬的阻断可防止肺泡纤维化,但不能防止细支气管纤维化。综上所述,
更新日期:2021-02-01
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