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Increased number and altered phenotype of lymphatic vessels in peripheral lung compartments of patients with COPD

BACKGROUND: De novo lymphatic vessel formation has recently been observed in lungs of patients with moderate chronic obstructive pulmonary disease (COPD). However, the distribution of lymphatic vessel changes among the anatomical compartments of diseased lungs is unknown. Furthermore, information re...

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Autores principales: Mori, Michiko, Andersson, Cecilia K, Graham, Gerard J, Löfdahl, Claes-Göran, Erjefält, Jonas S
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3728038/
https://www.ncbi.nlm.nih.gov/pubmed/23758732
http://dx.doi.org/10.1186/1465-9921-14-65
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author Mori, Michiko
Andersson, Cecilia K
Graham, Gerard J
Löfdahl, Claes-Göran
Erjefält, Jonas S
author_facet Mori, Michiko
Andersson, Cecilia K
Graham, Gerard J
Löfdahl, Claes-Göran
Erjefält, Jonas S
author_sort Mori, Michiko
collection PubMed
description BACKGROUND: De novo lymphatic vessel formation has recently been observed in lungs of patients with moderate chronic obstructive pulmonary disease (COPD). However, the distribution of lymphatic vessel changes among the anatomical compartments of diseased lungs is unknown. Furthermore, information regarding the nature of lymphatic vessel alterations across different stages of COPD is missing. This study performs a detailed morphometric characterization of lymphatic vessels in major peripheral lung compartments of patients with different severities of COPD and investigates the lymphatic expression of molecules involved in immune cell trafficking. METHODS: Peripheral lung resection samples obtained from patients with mild (GOLD stage I), moderate-severe (GOLD stage II-III), and very severe (GOLD stage IV) COPD were investigated for podoplanin-immunopositive lymphatic vessels in distinct peripheral lung compartments: bronchioles, pulmonary blood vessels and alveolar walls. Control subjects with normal lung function were divided into never smokers and smokers. Lymphatics were analysed by multiple morphological parameters, as well as for their expression of CCL21 and the chemokine scavenger receptor D6. RESULTS: The number of lymphatics increased by 133% in the alveolar parenchyma in patients with advanced COPD compared with never-smoking controls (p < 0.05). In patchy fibrotic lesions the number of alveolar lymphatics increased 20-fold from non-fibrotic parenchyma in the same COPD patients. The absolute number of lymphatics per bronchiole and artery was increased in advanced COPD, but numbers were not different after normalization to tissue area. Increased numbers of CCL21- and D6-positive lymphatics were observed in the alveolar parenchyma in advanced COPD compared with controls (p < 0.01). Lymphatic vessels also displayed increased mean levels of immunoreactivity for CCL21 in the wall of bronchioles (p < 0.01) and bronchiole-associated arteries (p < 0.05), as well as the alveolar parenchyma (p < 0.001) in patients with advanced COPD compared with never-smoking controls. A similar increase in lymphatic D6 immunoreactivity was observed in bronchioles (p < 0.05) and alveolar parenchyma (p < 0.01). CONCLUSIONS: This study shows that severe stages of COPD is associated with increased numbers of alveolar lymphatic vessels and a change in lymphatic vessel phenotype in major peripheral lung compartments. This novel histopathological feature is suggested to have important implications for distal lung immune cell traffic in advanced COPD.
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spelling pubmed-37280382013-07-31 Increased number and altered phenotype of lymphatic vessels in peripheral lung compartments of patients with COPD Mori, Michiko Andersson, Cecilia K Graham, Gerard J Löfdahl, Claes-Göran Erjefält, Jonas S Respir Res Research BACKGROUND: De novo lymphatic vessel formation has recently been observed in lungs of patients with moderate chronic obstructive pulmonary disease (COPD). However, the distribution of lymphatic vessel changes among the anatomical compartments of diseased lungs is unknown. Furthermore, information regarding the nature of lymphatic vessel alterations across different stages of COPD is missing. This study performs a detailed morphometric characterization of lymphatic vessels in major peripheral lung compartments of patients with different severities of COPD and investigates the lymphatic expression of molecules involved in immune cell trafficking. METHODS: Peripheral lung resection samples obtained from patients with mild (GOLD stage I), moderate-severe (GOLD stage II-III), and very severe (GOLD stage IV) COPD were investigated for podoplanin-immunopositive lymphatic vessels in distinct peripheral lung compartments: bronchioles, pulmonary blood vessels and alveolar walls. Control subjects with normal lung function were divided into never smokers and smokers. Lymphatics were analysed by multiple morphological parameters, as well as for their expression of CCL21 and the chemokine scavenger receptor D6. RESULTS: The number of lymphatics increased by 133% in the alveolar parenchyma in patients with advanced COPD compared with never-smoking controls (p < 0.05). In patchy fibrotic lesions the number of alveolar lymphatics increased 20-fold from non-fibrotic parenchyma in the same COPD patients. The absolute number of lymphatics per bronchiole and artery was increased in advanced COPD, but numbers were not different after normalization to tissue area. Increased numbers of CCL21- and D6-positive lymphatics were observed in the alveolar parenchyma in advanced COPD compared with controls (p < 0.01). Lymphatic vessels also displayed increased mean levels of immunoreactivity for CCL21 in the wall of bronchioles (p < 0.01) and bronchiole-associated arteries (p < 0.05), as well as the alveolar parenchyma (p < 0.001) in patients with advanced COPD compared with never-smoking controls. A similar increase in lymphatic D6 immunoreactivity was observed in bronchioles (p < 0.05) and alveolar parenchyma (p < 0.01). CONCLUSIONS: This study shows that severe stages of COPD is associated with increased numbers of alveolar lymphatic vessels and a change in lymphatic vessel phenotype in major peripheral lung compartments. This novel histopathological feature is suggested to have important implications for distal lung immune cell traffic in advanced COPD. BioMed Central 2013 2013-06-11 /pmc/articles/PMC3728038/ /pubmed/23758732 http://dx.doi.org/10.1186/1465-9921-14-65 Text en Copyright © 2013 Mori 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
Mori, Michiko
Andersson, Cecilia K
Graham, Gerard J
Löfdahl, Claes-Göran
Erjefält, Jonas S
Increased number and altered phenotype of lymphatic vessels in peripheral lung compartments of patients with COPD
title Increased number and altered phenotype of lymphatic vessels in peripheral lung compartments of patients with COPD
title_full Increased number and altered phenotype of lymphatic vessels in peripheral lung compartments of patients with COPD
title_fullStr Increased number and altered phenotype of lymphatic vessels in peripheral lung compartments of patients with COPD
title_full_unstemmed Increased number and altered phenotype of lymphatic vessels in peripheral lung compartments of patients with COPD
title_short Increased number and altered phenotype of lymphatic vessels in peripheral lung compartments of patients with COPD
title_sort increased number and altered phenotype of lymphatic vessels in peripheral lung compartments of patients with copd
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3728038/
https://www.ncbi.nlm.nih.gov/pubmed/23758732
http://dx.doi.org/10.1186/1465-9921-14-65
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