Surface PEGylation suppresses pulmonary effects of CuO in allergen-induced lung inflammation

Particle and Fibre Toxicology

Nicky Ehrlich¹  Kai Savolainen²  Henrik Wolff²  Harri Alenius³  Piia Karisola³  Joseph Ndika³  Marit Ilves³  Veer Marwah⁴  Dario Greco⁴  Pia Anneli Sofia Kinaret⁴  Vittorio Fortino⁴  Manuel Correia⁵  Katrin Loeschner⁵  Yuri Fedutik⁶  Joanne Vassallo⁷  Richard D. Handy⁷  Alexandros Besinis⁷ 

[1] Department of Chemical and Biochemical Engineering, Technical University of Denmark;Finnish Institute of Occupational Health;Human Microbiome Research Program, Faculty of Medicine, University of Helsinki;Institute of Biotechnology, University of Helsinki;National Food Institute, Technical University of Denmark;PlasmaChem GmbH;School of Biological and Marine Sciences, Faculty of Science and Engineering, University of Plymouth;

关键词: CuO;    Engineered nanomaterial;    Health effects;    Inflammation;    Asthma;    Allergic airway inflammation;   

DOI  :  10.1186/s12989-019-0309-1

来源: DOAJ

【 摘 要 】

Abstract Background 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 NH3) 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. Results 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 NH3 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. Conclusions 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.

【 授权许可】

Unknown