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Archives of Toxicology

, Volume 92, Issue 4, pp 1551–1561 | Cite as

Irritant-induced asthma to hypochlorite in mice due to impairment of the airway barrier

  • Sofie Van Den Broucke
  • Lore Pollaris
  • Greetje Vande Velde
  • Erik Verbeken
  • Benoit Nemery
  • Jeroen Vanoirbeek
  • Peter Hoet
Organ Toxicity and Mechanisms
  • 211 Downloads

Abstract

Inhalation of commonly present irritants, such as chlorine and chlorine derivatives, can cause adverse respiratory effects, including irritant-induced asthma (IIA). We hypothesize that due to airway barrier impairment, exposure to hypochlorite (ClO-) can result in airway hypersensitivity. C57Bl/6 mice received an intra-peritoneal (i.p.) injection of the airway damaging agent naphthalene (NA, 200 mg/kg body weight) or vehicle (mineral oil, MO). In vivo micro-computed tomography (CT) images of the lungs were acquired before and at regular time points after the i.p. treatment. After a recovery period of 14 days an intranasal (i.n.) challenge with 0.003% active chlorine (in ClO-) or vehicle (distilled water, H2O) was given, followed by assessment of the breathing frequency. One day later, pulmonary function, along with pulmonary inflammation was determined. Lung permeability was assessed by means of total broncho-alveolar lavage (BAL) protein content and plasma surfactant protein (SP)-D levels. In vivo micro-CT imaging revealed enlargement of the lungs and airways early after NA treatment, with a return to normal at day 14. When challenged i.n. with ClO-, NA-pretreated mice immediately responded with a sensory irritant response. Twenty-four hours later, NA/ClO- mice showed airway hyperreactivity (AHR), accompanied by a neutrophilic and eosinophilic inflammation. NA administration followed by ClO- induced airway barrier impairment, as shown by increased BAL protein and plasma SP-D concentrations; histology revealed epithelial denudation. These data prove that NA-induced lung impairment renders the lungs of mice more sensitive to an airway challenge with ClO-, confirming the hypothesis that incomplete barrier repair, followed by irritant exposure results in airway hypersensitivity.

Keywords

Irritants Asthma Airway damage Airway epithelium 

Notes

Acknowledgements

This project was supported by a grant from the University of Leuven Research Council (GOA/14/011, STG/15/024 and C24/17/061) and a grant of the Flemish Research Foundation (Research Grant 1504912N).

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

204_2018_2161_MOESM1_ESM.docx (27 kb)
Supplementary material 1 (DOCX 26 KB)
204_2018_2161_MOESM2_ESM.pptx (76 kb)
Supplementary material 2 (PPTX 76 KB)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Centre for Environment and Health, Department of Public Health and Primary CareUniversity of LeuvenLeuvenBelgium
  2. 2.Biomedical MRI Unit, Department of Imaging and PathologyUniversity of LeuvenLeuvenBelgium
  3. 3.Translational Cell and Tissue Research Unit, Department of Imaging and PathologyUniversity of LeuvenLeuvenBelgium

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