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吸入棒状碳纳米管会引发非传统的过敏性气道炎症。

Inhalation of rod-like carbon nanotubes causes unconventional allergic airway inflammation.

作者信息

Rydman Elina M, Ilves Marit, Koivisto Antti J, Kinaret Pia A S, Fortino Vittorio, Savinko Terhi S, Lehto Maili T, Pulkkinen Ville, Vippola Minnamari, Hämeri Kaarle J, Matikainen Sampsa, Wolff Henrik, Savolainen Kai M, Greco Dario, Alenius Harri

机构信息

Nanosafety Research Centre, Finnish Institute of Occupational Health, Helsinki, Finland.

Pulmonary Division, Department of Medicine, University of Helsinki, Helsinki, Finland.

出版信息

Part Fibre Toxicol. 2014 Oct 16;11:48. doi: 10.1186/s12989-014-0048-2.

Abstract

BACKGROUND

Carbon nanotubes (CNT) represent a great promise for technological and industrial development but serious concerns on their health effects have also emerged. Rod-shaped CNT are, in fact, able to induce asbestos-like pathogenicity in mice including granuloma formation in abdominal cavity and sub-pleural fibrosis. Exposure to CNT, especially in the occupational context, happens mainly by inhalation. However, little is known about the possible effects of CNT on pulmonary allergic diseases, such as asthma.

METHODS

We exposed mice by inhalation to two types of multi-walled CNT, rigid rod-like and flexible tangled CNT, for four hours a day once or on four consecutive days. Early events were monitored immediately and 24 hours after the single inhalation exposure and the four day exposure mimicked an occupational work week. Mast cell deficient mice were used to evaluate the role of mast cells in the occurring inflammation.

RESULTS

Here we show that even a short-term inhalation of the rod-like CNT induces novel innate immunity-mediated allergic-like airway inflammation in healthy mice. Marked eosinophilia was accompanied by mucus hypersecretion, AHR and the expression of Th2-type cytokines. Exploration of the early events by transcriptomics analysis reveals that a single 4-h exposure to rod-shaped CNT, but not to tangled CNT, causes a radical up-regulation of genes involved in innate immunity and cytokine/chemokine pathways. Mast cells were found to partially regulate the inflammation caused by rod-like CNT, but also alveaolar macrophages play an important role in the early stages.

CONCLUSIONS

These observations emphasize the diverse abilities of CNT to impact the immune system, and they should be taken into account for hazard assessment.

摘要

背景

碳纳米管(CNT)对技术和工业发展具有巨大潜力,但人们也对其健康影响深感担忧。事实上,棒状碳纳米管能够在小鼠体内诱发类似石棉的致病性,包括腹腔肉芽肿形成和胸膜下纤维化。接触碳纳米管,尤其是在职业环境中,主要通过吸入发生。然而,关于碳纳米管对肺部过敏性疾病(如哮喘)的可能影响知之甚少。

方法

我们让小鼠每天吸入两种多壁碳纳米管,即刚性棒状碳纳米管和柔性缠结碳纳米管,每天4小时,单次或连续4天。在单次吸入暴露后以及模拟职业工作周的4天暴露后立即和24小时监测早期事件。使用肥大细胞缺陷小鼠评估肥大细胞在发生的炎症中的作用。

结果

我们在此表明,即使短期吸入棒状碳纳米管也会在健康小鼠中诱发新型先天免疫介导的过敏性气道炎症。明显的嗜酸性粒细胞增多伴随着黏液分泌过多、气道高反应性和Th2型细胞因子的表达。通过转录组学分析对早期事件的探索表明,单次4小时暴露于棒状碳纳米管而非缠结碳纳米管会导致参与先天免疫和细胞因子/趋化因子途径的基因显著上调。发现肥大细胞部分调节由棒状碳纳米管引起的炎症,但肺泡巨噬细胞在早期也起重要作用。

结论

这些观察结果强调了碳纳米管影响免疫系统的多种能力,在危害评估中应予以考虑。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d1c/4215016/28ffe5c5ac2d/12989_2014_48_Fig1_HTML.jpg

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