Pneumologie 2018; 72(07): 536
DOI: 10.1055/s-0038-1660918
Abstracts
Georg Thieme Verlag KG Stuttgart · New York

Low level Carbon Black nanoparticle (CBNP) exposure of the lung does not aggravate experimental asthma in mice

S Webering
1   Research Center Borstel, Priority Area Asthma & Allergy, Division of Experimental Pneumology, Borstel
3   Airway Research Center North (ARCN), German Center for Lung Research (DZL)
,
K Lindner
2   Institute of Anatomy, University of Lübeck (UzL), Lübeck
3   Airway Research Center North (ARCN), German Center for Lung Research (DZL)
,
P König
2   Institute of Anatomy, University of Lübeck (UzL), Lübeck
3   Airway Research Center North (ARCN), German Center for Lung Research (DZL)
,
H Fehrenbach
1   Research Center Borstel, Priority Area Asthma & Allergy, Division of Experimental Pneumology, Borstel
3   Airway Research Center North (ARCN), German Center for Lung Research (DZL)
4   Leibniz Research Association Nanosafety, Leibniz Association, Berlin, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
10 July 2018 (online)

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Introduction:

Asthma is a multifactorial lung disease characterized by airway hyperresponsiveness (AHR), remodeling, and inflammation. Allergic bronchial asthma develops following sensitization to an allergen and subsequent local allergen challenge. Exposure of diseased lungs with a 2nd trigger such as respiratory viruses, bacteria or particulate matter can result in an acute aggravation of the disease (exacerbation). We investigated the potential of CBNPs to induce an aggravation of asthma-related effects in an ex vivo and an in vivo experimental model.

Methods:

We used Printex®90 (P90) as reference particles and P90 coated on the surface with Benzo[a]pyren (P90-BaP) or 9-Nitroanthracen. Additionally, we analyzed a soot from acetylene combustion, the surface of which is covered with a mixture of polycyclic aromatic hydrocarbons (AS-PAH) and that exhibited mild effects in healthy mice. All CBNPs were recently shown to exhibit similar hydrodynamic diameter and zeta-potential in suspension [Lindner et al. Part Fibre Toxicol. 2017;14(1):8]. In the in vivo mouse model, wild-type mice were sensitized to ovalbumin (OVA) and challenged with OVA aerosol on 3 consecutive days. CBNPs were applied by oropharyngeal aspiration (70 µl, 100 ng/µl) prior to the 3rd challenge and 24 hours later. AHR, number of immune cells, TH2-cytokine levels in BAL fluid, and mucus production were analyzed. In the ex vivo explanted murine trachea, we analyzed cilia-driven particle transport, cell death, and mucus release as well as mRNA expression of markers for PAH metabolism (Cyp1a1, Cyp1b1), oxidative stress (Gr, Gpx3), and mucin Muc5ac.

Results:

In mice with experimental allergic asthma, we showed that CBNP exposure neither affected AHR, nor BAL cytokine levels or infiltration of leukocytes into the airways. In the trachea, particle transport speed and number of necrotic epithelial cells were similar in all the OVA/CBNP groups and the OVA-control group. Only P90 decreased ciliary beat frequency, which may relate to enhanced mucus release indicated by increased Muc5ac mRNA expression compared to OVA-controls. mRNA expression of Cyp1a1, Cyp1b1, Gr and Gpx-3 in tracheal epithelium was not affected. In distal airways, mRNA expression of Cyp1a1, Cyp1b1, Gr and Gpx-3 were slightly increased by P90-BaP and AS-PAH compared to OVA-controls.

Conclusion:

Our results demonstrate that low level exposure with all four tested CBNP did not aggravate experimental allergic asthma in mice. This was independent of surface PAHs.

Acknowledgments:

Supported by grant of the BMBF (NanoCare 3.0, Project: nanoCOLT).

*equally contributing authors