Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, 00290, Helsinki, Finland.
Institute of Biotechnology, University of Helsinki, 00790, Helsinki, Finland.
Part Fibre Toxicol. 2019 Jul 5;16(1):28. doi: 10.1186/s12989-019-0309-1.
Copper oxide (CuO) nanomaterials are used in a wide range of industrial and commercial applications. These materials can be hazardous, especially if they are inhaled. As a result, the pulmonary effects of CuO nanomaterials have been studied in healthy subjects but limited knowledge exists today about their effects on lungs with allergic airway inflammation (AAI). The objective of this study was to investigate how pristine CuO modulates allergic lung inflammation and whether surface modifications can influence its reactivity. CuO and its carboxylated (CuO COOH), methylaminated (CuO NH) and PEGylated (CuO PEG) derivatives were administered here on four consecutive days via oropharyngeal aspiration in a mouse model of AAI. Standard genome-wide gene expression profiling as well as conventional histopathological and immunological methods were used to investigate the modulatory effects of the nanomaterials on both healthy and compromised immune system.
Our data demonstrates that although CuO materials did not considerably influence hallmarks of allergic airway inflammation, the materials exacerbated the existing lung inflammation by eliciting dramatic pulmonary neutrophilia. Transcriptomic analysis showed that CuO, CuO COOH and CuO NH commonly enriched neutrophil-related biological processes, especially in healthy mice. In sharp contrast, CuO PEG had a significantly lower potential in triggering changes in lungs of healthy and allergic mice revealing that surface PEGylation suppresses the effects triggered by the pristine material.
CuO as well as its functionalized forms worsen allergic airway inflammation by causing neutrophilia in the lungs, however, our results also show that surface PEGylation can be a promising approach for inhibiting the effects of pristine CuO. Our study provides information for health and safety assessment of modified CuO materials, and it can be useful in the development of nanomedical applications.
氧化铜 (CuO) 纳米材料广泛应用于工业和商业领域。这些材料可能具有危害性，尤其是吸入后。因此，人们研究了健康受试者肺部吸入氧化铜纳米材料的影响，但目前对于氧化铜纳米材料对过敏性气道炎症 (AAI) 肺部的影响知之甚少。本研究旨在探讨原始氧化铜如何调节过敏性肺炎症，以及表面修饰是否会影响其反应性。在此，通过口咽部吸入将氧化铜及其羧基化 (CuO COOH)、甲基氨基化 (CuO NH) 和聚乙二醇化 (CuO PEG) 衍生物连续四天给药于 AAI 小鼠模型中。使用标准全基因组基因表达谱分析以及常规组织病理学和免疫学方法，研究纳米材料对健康和受损免疫系统的调节作用。
我们的数据表明，尽管氧化铜材料对过敏性气道炎症的标志性特征没有显著影响，但它们通过引起剧烈的肺部中性粒细胞增多，加剧了现有的肺部炎症。转录组分析表明，氧化铜、氧化铜 COOH 和氧化铜 NH 通常富集与中性粒细胞相关的生物学过程，尤其是在健康小鼠中。相比之下，CuO PEG 对健康和过敏性小鼠肺部引发变化的潜力明显较低，表明表面聚乙二醇化抑制了原始材料引发的作用。
氧化铜及其功能化形式通过引起肺部中性粒细胞增多，加重过敏性气道炎症，然而，我们的结果还表明，表面聚乙二醇化可能是抑制原始氧化铜作用的有前途的方法。我们的研究为改性氧化铜材料的健康和安全评估提供了信息，并且可用于纳米医学应用的开发。
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