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Cigarette smoke-induced pulmonary emphysema in scid-mice. Is the acquired immune system required?

BACKGROUND: Chronic obstructive pulmonary disease is associated with a chronic inflammatory response of the host to chronic exposure to inhaled toxic gases and particles. Although inflammatory cells of both the innate and adaptive immune system infiltrate the lungs in pulmonary emphysema and form ly...

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Autores principales: D'hulst, An I, Maes, Tania, Bracke, Ken R, Demedts, Ingel K, Tournoy, Kurt G, Joos, Guy F, Brusselle, Guy G
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1334210/
https://www.ncbi.nlm.nih.gov/pubmed/16359546
http://dx.doi.org/10.1186/1465-9921-6-147
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author D'hulst, An I
Maes, Tania
Bracke, Ken R
Demedts, Ingel K
Tournoy, Kurt G
Joos, Guy F
Brusselle, Guy G
author_facet D'hulst, An I
Maes, Tania
Bracke, Ken R
Demedts, Ingel K
Tournoy, Kurt G
Joos, Guy F
Brusselle, Guy G
author_sort D'hulst, An I
collection PubMed
description BACKGROUND: Chronic obstructive pulmonary disease is associated with a chronic inflammatory response of the host to chronic exposure to inhaled toxic gases and particles. Although inflammatory cells of both the innate and adaptive immune system infiltrate the lungs in pulmonary emphysema and form lymphoid follicles around the small airways, the exact role of the acquired immune system in the pathogenesis of emphysema is not known. METHODS: In this study, wild type Balb/c mice and immunodeficient scid mice – which lack functional B- and T-cells – were exposed to mainstream cigarette smoke (CS) for 5 weeks or 6 months. RESULTS: Subacute CS-exposure for 5 weeks significantly increased innate inflammatory cells (neutrophils, macrophages and dendritic cells) in the bronchoalveolar lavage (BAL) fluid of wild type mice and scid mice, which correlated with the CS-induced upregulation of the chemokines Monocyte Chemotactic Protein-1, Macrophage Inflammatory Protein-3α and KC (= mouse Interleukin-8). Chronic CS-exposure for 6 months significantly increased the number of neutrophils, macrophages, dendritic cells, CD4(+ )and CD8(+ )T-lymphocytes in BAL fluid and lungs of wild type mice compared to air-exposed littermates, and augmented the size and number of peribronchial lymphoid follicles. In contrast, neither B-lymphocytes, nor T-lymphocytes, nor lymphoid follicles could be discerned in the lungs of air- or CS-exposed scid mice. Importantly, chronic CS-exposure induced pulmonary emphysema in both wild type animals and scid mice, as evidenced by a significant increase in the mean linear intercept and the destructive index of CS-exposed versus air-exposed animals. The CS-induced emphysema was associated with increased mRNA expression of matrix metalloproteinase-12 in the lungs and increased protein levels of Tumor Necrosis Factor-α in the BAL fluid of CS-exposed Balb/c and scid mice compared to air-exposed littermates. CONCLUSION: This study suggests that the adaptive immune system is not required per se to develop pulmonary emphysema in response to chronic CS-exposure, since emphysema can be induced in scid mice, which lack lymphoid follicles as well as functional B- and T-cells.
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spelling pubmed-13342102006-01-19 Cigarette smoke-induced pulmonary emphysema in scid-mice. Is the acquired immune system required? D'hulst, An I Maes, Tania Bracke, Ken R Demedts, Ingel K Tournoy, Kurt G Joos, Guy F Brusselle, Guy G Respir Res Research BACKGROUND: Chronic obstructive pulmonary disease is associated with a chronic inflammatory response of the host to chronic exposure to inhaled toxic gases and particles. Although inflammatory cells of both the innate and adaptive immune system infiltrate the lungs in pulmonary emphysema and form lymphoid follicles around the small airways, the exact role of the acquired immune system in the pathogenesis of emphysema is not known. METHODS: In this study, wild type Balb/c mice and immunodeficient scid mice – which lack functional B- and T-cells – were exposed to mainstream cigarette smoke (CS) for 5 weeks or 6 months. RESULTS: Subacute CS-exposure for 5 weeks significantly increased innate inflammatory cells (neutrophils, macrophages and dendritic cells) in the bronchoalveolar lavage (BAL) fluid of wild type mice and scid mice, which correlated with the CS-induced upregulation of the chemokines Monocyte Chemotactic Protein-1, Macrophage Inflammatory Protein-3α and KC (= mouse Interleukin-8). Chronic CS-exposure for 6 months significantly increased the number of neutrophils, macrophages, dendritic cells, CD4(+ )and CD8(+ )T-lymphocytes in BAL fluid and lungs of wild type mice compared to air-exposed littermates, and augmented the size and number of peribronchial lymphoid follicles. In contrast, neither B-lymphocytes, nor T-lymphocytes, nor lymphoid follicles could be discerned in the lungs of air- or CS-exposed scid mice. Importantly, chronic CS-exposure induced pulmonary emphysema in both wild type animals and scid mice, as evidenced by a significant increase in the mean linear intercept and the destructive index of CS-exposed versus air-exposed animals. The CS-induced emphysema was associated with increased mRNA expression of matrix metalloproteinase-12 in the lungs and increased protein levels of Tumor Necrosis Factor-α in the BAL fluid of CS-exposed Balb/c and scid mice compared to air-exposed littermates. CONCLUSION: This study suggests that the adaptive immune system is not required per se to develop pulmonary emphysema in response to chronic CS-exposure, since emphysema can be induced in scid mice, which lack lymphoid follicles as well as functional B- and T-cells. BioMed Central 2005 2005-12-16 /pmc/articles/PMC1334210/ /pubmed/16359546 http://dx.doi.org/10.1186/1465-9921-6-147 Text en Copyright © 2005 D'hulst 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 cited.
spellingShingle Research
D'hulst, An I
Maes, Tania
Bracke, Ken R
Demedts, Ingel K
Tournoy, Kurt G
Joos, Guy F
Brusselle, Guy G
Cigarette smoke-induced pulmonary emphysema in scid-mice. Is the acquired immune system required?
title Cigarette smoke-induced pulmonary emphysema in scid-mice. Is the acquired immune system required?
title_full Cigarette smoke-induced pulmonary emphysema in scid-mice. Is the acquired immune system required?
title_fullStr Cigarette smoke-induced pulmonary emphysema in scid-mice. Is the acquired immune system required?
title_full_unstemmed Cigarette smoke-induced pulmonary emphysema in scid-mice. Is the acquired immune system required?
title_short Cigarette smoke-induced pulmonary emphysema in scid-mice. Is the acquired immune system required?
title_sort cigarette smoke-induced pulmonary emphysema in scid-mice. is the acquired immune system required?
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1334210/
https://www.ncbi.nlm.nih.gov/pubmed/16359546
http://dx.doi.org/10.1186/1465-9921-6-147
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