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Smoking Is Associated with Shortened Airway Cilia

BACKGROUND: Whereas cilia damage and reduced cilia beat frequency have been implicated as causative of reduced mucociliary clearance in smokers, theoretically mucociliary clearance could also be affected by cilia length. Based on models of mucociliary clearance predicting that cilia length must exce...

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Autores principales: Leopold, Philip L., O'Mahony, Michael J., Lian, X. Julie, Tilley, Ann E., Harvey, Ben-Gary, Crystal, Ronald G.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2790614/
https://www.ncbi.nlm.nih.gov/pubmed/20016779
http://dx.doi.org/10.1371/journal.pone.0008157
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author Leopold, Philip L.
O'Mahony, Michael J.
Lian, X. Julie
Tilley, Ann E.
Harvey, Ben-Gary
Crystal, Ronald G.
author_facet Leopold, Philip L.
O'Mahony, Michael J.
Lian, X. Julie
Tilley, Ann E.
Harvey, Ben-Gary
Crystal, Ronald G.
author_sort Leopold, Philip L.
collection PubMed
description BACKGROUND: Whereas cilia damage and reduced cilia beat frequency have been implicated as causative of reduced mucociliary clearance in smokers, theoretically mucociliary clearance could also be affected by cilia length. Based on models of mucociliary clearance predicting that cilia length must exceed the 6–7 µm airway surface fluid depth to generate force in the mucus layer, we hypothesized that cilia height may be decreased in airway epithelium of normal smokers compared to nonsmokers. METHODOLOGY/PRINCIPAL FINDINGS: Cilia length in normal nonsmokers and smokers was evaluated in aldehyde-fixed, paraffin-embedded endobronchial biopsies, and air-dried and hydrated samples were brushed from human airway epithelium via fiberoptic bronchoscopy. In 28 endobronchial biopsies, healthy smoker cilia length was reduced by 15% compared to nonsmokers (p<0.05). In 39 air-dried samples of airway epithelial cells, smoker cilia length was reduced by 13% compared to nonsmokers (p<0.0001). Analysis of the length of individual, detached cilia in 27 samples showed that smoker cilia length was reduced by 9% compared to nonsmokers (p<0.05). Finally, in 16 fully hydrated, unfixed samples, smoker cilia length was reduced 7% compared to nonsmokers (p<0.05). Using genome-wide analysis of airway epithelial gene expression we identified 6 cilia-related genes whose expression levels were significantly reduced in healthy smokers compared to healthy nonsmokers. CONCLUSIONS/SIGNIFICANCE: Models predict that a reduction in cilia length would reduce mucociliary clearance, suggesting that smoking-associated shorter airway epithelial cilia play a significant role in the pathogenesis of smoking-induced lung disease.
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spelling pubmed-27906142009-12-17 Smoking Is Associated with Shortened Airway Cilia Leopold, Philip L. O'Mahony, Michael J. Lian, X. Julie Tilley, Ann E. Harvey, Ben-Gary Crystal, Ronald G. PLoS One Research Article BACKGROUND: Whereas cilia damage and reduced cilia beat frequency have been implicated as causative of reduced mucociliary clearance in smokers, theoretically mucociliary clearance could also be affected by cilia length. Based on models of mucociliary clearance predicting that cilia length must exceed the 6–7 µm airway surface fluid depth to generate force in the mucus layer, we hypothesized that cilia height may be decreased in airway epithelium of normal smokers compared to nonsmokers. METHODOLOGY/PRINCIPAL FINDINGS: Cilia length in normal nonsmokers and smokers was evaluated in aldehyde-fixed, paraffin-embedded endobronchial biopsies, and air-dried and hydrated samples were brushed from human airway epithelium via fiberoptic bronchoscopy. In 28 endobronchial biopsies, healthy smoker cilia length was reduced by 15% compared to nonsmokers (p<0.05). In 39 air-dried samples of airway epithelial cells, smoker cilia length was reduced by 13% compared to nonsmokers (p<0.0001). Analysis of the length of individual, detached cilia in 27 samples showed that smoker cilia length was reduced by 9% compared to nonsmokers (p<0.05). Finally, in 16 fully hydrated, unfixed samples, smoker cilia length was reduced 7% compared to nonsmokers (p<0.05). Using genome-wide analysis of airway epithelial gene expression we identified 6 cilia-related genes whose expression levels were significantly reduced in healthy smokers compared to healthy nonsmokers. CONCLUSIONS/SIGNIFICANCE: Models predict that a reduction in cilia length would reduce mucociliary clearance, suggesting that smoking-associated shorter airway epithelial cilia play a significant role in the pathogenesis of smoking-induced lung disease. Public Library of Science 2009-12-16 /pmc/articles/PMC2790614/ /pubmed/20016779 http://dx.doi.org/10.1371/journal.pone.0008157 Text en Leopold et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Leopold, Philip L.
O'Mahony, Michael J.
Lian, X. Julie
Tilley, Ann E.
Harvey, Ben-Gary
Crystal, Ronald G.
Smoking Is Associated with Shortened Airway Cilia
title Smoking Is Associated with Shortened Airway Cilia
title_full Smoking Is Associated with Shortened Airway Cilia
title_fullStr Smoking Is Associated with Shortened Airway Cilia
title_full_unstemmed Smoking Is Associated with Shortened Airway Cilia
title_short Smoking Is Associated with Shortened Airway Cilia
title_sort smoking is associated with shortened airway cilia
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2790614/
https://www.ncbi.nlm.nih.gov/pubmed/20016779
http://dx.doi.org/10.1371/journal.pone.0008157
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