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Biokinetics of nanoparticles and susceptibility to particulate exposure in a murine model of cystic fibrosis
BACKGROUND: Persons with cystic fibrosis (CF) are at-risk for health effects from ambient air pollution but little is known about the interaction of nanoparticles (NP) with CF lungs. Here we study the distribution of inhaled NP in a murine CF model and aim to reveal mechanisms contributing to advers...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4008490/ https://www.ncbi.nlm.nih.gov/pubmed/24758489 http://dx.doi.org/10.1186/1743-8977-11-19 |
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author | Geiser, Marianne Stoeger, Tobias Casaulta, Marco Chen, Shanze Semmler-Behnke, Manuela Bolle, Ines Takenaka, Shinji Kreyling, Wolfgang G Schulz, Holger |
author_facet | Geiser, Marianne Stoeger, Tobias Casaulta, Marco Chen, Shanze Semmler-Behnke, Manuela Bolle, Ines Takenaka, Shinji Kreyling, Wolfgang G Schulz, Holger |
author_sort | Geiser, Marianne |
collection | PubMed |
description | BACKGROUND: Persons with cystic fibrosis (CF) are at-risk for health effects from ambient air pollution but little is known about the interaction of nanoparticles (NP) with CF lungs. Here we study the distribution of inhaled NP in a murine CF model and aim to reveal mechanisms contributing to adverse effects of inhaled particles in susceptible populations. METHODS: Chloride channel defective Cftr(TgH (neoim) Hgu) mice were used to analyze lung function, lung distribution and whole body biokinetics of inhaled NP, and inflammatory responses after intratracheal administration of NP. Distribution of 20-nm titanium dioxide NP in lungs was assessed on ultrathin sections immediately and 24 h after a one-hour NP inhalation. NP biokinetics was deduced from total and regional lung deposition and from whole body translocation of inhaled 30-nm iridium NP within 24 h after aerosol inhalation. Inflammatory responses were assessed within 7 days after carbon NP instillation. RESULTS: Cftr mutant females had moderately reduced lung compliance and slightly increased airway resistance compared to wild type mice. We found no genotype dependent differences in total, regional and head deposition or in secondary-organ translocation of inhaled iridium NP. Titanium dioxide inhalation resulted in higher NP uptake by alveolar epithelial cells in Cftr mutants. Instillation of carbon NP induced a comparable acute and transient inflammatory response in both genotypes. The twofold increase of bronchoalveolar lavage (BAL) neutrophils in Cftr mutant compared to wild type mice at day 3 but not at days 1 and 7, indicated an impaired capacity in inflammation resolution in Cftr mutants. Concomitant to the delayed decline of neutrophils, BAL granulocyte-colony stimulating factor was augmented in Cftr mutant mice. Anti-inflammatory 15-hydroxyeicosatetraenoic acid was generally significantly lower in BAL of Cftr mutant than in wild type mice. CONCLUSIONS: Despite lacking alterations in lung deposition and biokinetics of inhaled NP, and absence of significant differences in lung function, higher uptake of NP by alveolar epithelial cells and prolonged, acute inflammatory responses to NP exposure indicate a moderately increased susceptibility of lungs to adverse effects of inhaled NP in Cftr mutant mice and provides potential mechanisms for the increased susceptibility of CF patients to air pollution. |
format | Online Article Text |
id | pubmed-4008490 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-40084902014-05-03 Biokinetics of nanoparticles and susceptibility to particulate exposure in a murine model of cystic fibrosis Geiser, Marianne Stoeger, Tobias Casaulta, Marco Chen, Shanze Semmler-Behnke, Manuela Bolle, Ines Takenaka, Shinji Kreyling, Wolfgang G Schulz, Holger Part Fibre Toxicol Research BACKGROUND: Persons with cystic fibrosis (CF) are at-risk for health effects from ambient air pollution but little is known about the interaction of nanoparticles (NP) with CF lungs. Here we study the distribution of inhaled NP in a murine CF model and aim to reveal mechanisms contributing to adverse effects of inhaled particles in susceptible populations. METHODS: Chloride channel defective Cftr(TgH (neoim) Hgu) mice were used to analyze lung function, lung distribution and whole body biokinetics of inhaled NP, and inflammatory responses after intratracheal administration of NP. Distribution of 20-nm titanium dioxide NP in lungs was assessed on ultrathin sections immediately and 24 h after a one-hour NP inhalation. NP biokinetics was deduced from total and regional lung deposition and from whole body translocation of inhaled 30-nm iridium NP within 24 h after aerosol inhalation. Inflammatory responses were assessed within 7 days after carbon NP instillation. RESULTS: Cftr mutant females had moderately reduced lung compliance and slightly increased airway resistance compared to wild type mice. We found no genotype dependent differences in total, regional and head deposition or in secondary-organ translocation of inhaled iridium NP. Titanium dioxide inhalation resulted in higher NP uptake by alveolar epithelial cells in Cftr mutants. Instillation of carbon NP induced a comparable acute and transient inflammatory response in both genotypes. The twofold increase of bronchoalveolar lavage (BAL) neutrophils in Cftr mutant compared to wild type mice at day 3 but not at days 1 and 7, indicated an impaired capacity in inflammation resolution in Cftr mutants. Concomitant to the delayed decline of neutrophils, BAL granulocyte-colony stimulating factor was augmented in Cftr mutant mice. Anti-inflammatory 15-hydroxyeicosatetraenoic acid was generally significantly lower in BAL of Cftr mutant than in wild type mice. CONCLUSIONS: Despite lacking alterations in lung deposition and biokinetics of inhaled NP, and absence of significant differences in lung function, higher uptake of NP by alveolar epithelial cells and prolonged, acute inflammatory responses to NP exposure indicate a moderately increased susceptibility of lungs to adverse effects of inhaled NP in Cftr mutant mice and provides potential mechanisms for the increased susceptibility of CF patients to air pollution. BioMed Central 2014-04-24 /pmc/articles/PMC4008490/ /pubmed/24758489 http://dx.doi.org/10.1186/1743-8977-11-19 Text en Copyright © 2014 Geiser et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. 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. |
spellingShingle | Research Geiser, Marianne Stoeger, Tobias Casaulta, Marco Chen, Shanze Semmler-Behnke, Manuela Bolle, Ines Takenaka, Shinji Kreyling, Wolfgang G Schulz, Holger Biokinetics of nanoparticles and susceptibility to particulate exposure in a murine model of cystic fibrosis |
title | Biokinetics of nanoparticles and susceptibility to particulate exposure in a murine model of cystic fibrosis |
title_full | Biokinetics of nanoparticles and susceptibility to particulate exposure in a murine model of cystic fibrosis |
title_fullStr | Biokinetics of nanoparticles and susceptibility to particulate exposure in a murine model of cystic fibrosis |
title_full_unstemmed | Biokinetics of nanoparticles and susceptibility to particulate exposure in a murine model of cystic fibrosis |
title_short | Biokinetics of nanoparticles and susceptibility to particulate exposure in a murine model of cystic fibrosis |
title_sort | biokinetics of nanoparticles and susceptibility to particulate exposure in a murine model of cystic fibrosis |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4008490/ https://www.ncbi.nlm.nih.gov/pubmed/24758489 http://dx.doi.org/10.1186/1743-8977-11-19 |
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