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

Marit Ilves; Pia Anneli Sofia Kinaret; Joseph Ndika; Piia Karisola; Veer Marwah; Vittorio Fortino; Yuri Fedutik; Manuel Correia; Nicky Ehrlich; Katrin Löschner; Alexandros Besinis; Joanne Vassallo; Richard D Handy; Henrik Wolff; Kai Savolainen; Dario Greco; Harri Alenius

doi:10.1186/s12989-019-0309-1

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

Marit Ilves, Pia Anneli Sofia Kinaret, Joseph Ndika, Piia Karisola, Veer Marwah, Vittorio Fortino, Yuri Fedutik, Manuel Correia, Nicky Ehrlich, Katrin Löschner, Alexandros Besinis, Joanne Vassallo, Richard D Handy, Henrik Wolff, Kai Savolainen, Dario Greco, Harri Alenius^*

^*Corresponding author for this work

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Abstract

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. 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. 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.

Original language	English
Article number	28
Journal	Particle and Fibre Toxicology
Volume	16
Number of pages	21
ISSN	1743-8977
DOIs	https://doi.org/10.1186/s12989-019-0309-1
Publication status	Published - 2019

Bibliographical note

© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Keywords

Allergic airway inflammation
Asthma
CuO
Engineered nanomaterial
Health effects
Inflammation
Risk assessment

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Ilves, M., Kinaret, P. A. S., Ndika, J., Karisola, P., Marwah, V., Fortino, V., Fedutik, Y., Correia, M., Ehrlich, N., Löschner, K., Besinis, A., Vassallo, J., Handy, R. D., Wolff, H., Savolainen, K., Greco, D., & Alenius, H. (2019). Surface PEGylation suppresses pulmonary effects of CuO in allergen-induced lung inflammation. Particle and Fibre Toxicology, 16, Article 28. https://doi.org/10.1186/s12989-019-0309-1

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abstract = "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. 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. 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.",

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note = "{\textcopyright} The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.",

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Ilves, M, Kinaret, PAS, Ndika, J, Karisola, P, Marwah, V, Fortino, V, Fedutik, Y, Correia, M, Ehrlich, N, Löschner, K, Besinis, A, Vassallo, J, Handy, RD, Wolff, H, Savolainen, K, Greco, D & Alenius, H 2019, 'Surface PEGylation suppresses pulmonary effects of CuO in allergen-induced lung inflammation', Particle and Fibre Toxicology, vol. 16, 28. https://doi.org/10.1186/s12989-019-0309-1

TY - JOUR

T1 - Surface PEGylation suppresses pulmonary effects of CuO in allergen-induced lung inflammation

AU - Ilves, Marit

AU - Kinaret, Pia Anneli Sofia

AU - Ndika, Joseph

AU - Karisola, Piia

AU - Marwah, Veer

AU - Fortino, Vittorio

AU - Fedutik, Yuri

AU - Correia, Manuel

AU - Ehrlich, Nicky

AU - Löschner, Katrin

AU - Besinis, Alexandros

AU - Vassallo, Joanne

AU - Handy, Richard D

AU - Wolff, Henrik

AU - Savolainen, Kai

AU - Greco, Dario

AU - Alenius, Harri

N1 - © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

PY - 2019

Y1 - 2019

N2 - 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. 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. 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.

AB - 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. 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. 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.

KW - Allergic airway inflammation

KW - Asthma

KW - CuO

KW - Engineered nanomaterial

KW - Health effects

KW - Inflammation

KW - Risk assessment

U2 - 10.1186/s12989-019-0309-1

DO - 10.1186/s12989-019-0309-1

M3 - Journal article

C2 - 31277695

SN - 1743-8977

VL - 16

JO - Particle and Fibre Toxicology

JF - Particle and Fibre Toxicology

M1 - 28

ER -

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

Abstract

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Keywords

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