Abundance of Non-Polarized Lung Macrophages with Poor Phagocytic Function in Chronic Obstructive Pulmonary Disease (COPD)
Lung macrophages are the key immune effector cells in the pathogenesis of Chronic Obstructive Pulmonary Disease (COPD). Several studies have shown an increase in their numbers in bronchoalveolar lavage fluid (BAL) of subjects with COPD compared to controls, suggesting a pathogenic role in disease in...
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MDPI AG
2020-10-01
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Series: | Biomedicines |
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Online Access: | https://www.mdpi.com/2227-9059/8/10/398 |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kentaro Akata Kei Yamasaki Fernando Sergio Leitao Filho Chen Xi Yang Hiroto Takiguchi Basak Sahin Beth A Whalen Cheng Wei Tony Yang Janice M Leung Don D Sin Stephanus van Eeden |
spellingShingle |
Kentaro Akata Kei Yamasaki Fernando Sergio Leitao Filho Chen Xi Yang Hiroto Takiguchi Basak Sahin Beth A Whalen Cheng Wei Tony Yang Janice M Leung Don D Sin Stephanus van Eeden Abundance of Non-Polarized Lung Macrophages with Poor Phagocytic Function in Chronic Obstructive Pulmonary Disease (COPD) Biomedicines macrophages phagocytosis COPD phenotype inflammation |
author_facet |
Kentaro Akata Kei Yamasaki Fernando Sergio Leitao Filho Chen Xi Yang Hiroto Takiguchi Basak Sahin Beth A Whalen Cheng Wei Tony Yang Janice M Leung Don D Sin Stephanus van Eeden |
author_sort |
Kentaro Akata |
title |
Abundance of Non-Polarized Lung Macrophages with Poor Phagocytic Function in Chronic Obstructive Pulmonary Disease (COPD) |
title_short |
Abundance of Non-Polarized Lung Macrophages with Poor Phagocytic Function in Chronic Obstructive Pulmonary Disease (COPD) |
title_full |
Abundance of Non-Polarized Lung Macrophages with Poor Phagocytic Function in Chronic Obstructive Pulmonary Disease (COPD) |
title_fullStr |
Abundance of Non-Polarized Lung Macrophages with Poor Phagocytic Function in Chronic Obstructive Pulmonary Disease (COPD) |
title_full_unstemmed |
Abundance of Non-Polarized Lung Macrophages with Poor Phagocytic Function in Chronic Obstructive Pulmonary Disease (COPD) |
title_sort |
abundance of non-polarized lung macrophages with poor phagocytic function in chronic obstructive pulmonary disease (copd) |
publisher |
MDPI AG |
series |
Biomedicines |
issn |
2227-9059 |
publishDate |
2020-10-01 |
description |
Lung macrophages are the key immune effector cells in the pathogenesis of Chronic Obstructive Pulmonary Disease (COPD). Several studies have shown an increase in their numbers in bronchoalveolar lavage fluid (BAL) of subjects with COPD compared to controls, suggesting a pathogenic role in disease initiation and progression. Although reduced lung macrophage phagocytic ability has been previously shown in COPD, the relationship between lung macrophages’ phenotypic characteristics and functional properties in COPD is still unclear. (1) Methods: Macrophages harvested from bronchoalveolar lavage (BAL) fluid of subjects with and without COPD (GOLD grades, I–III) were immuno-phenotyped, and their function and gene expression profiles were assessed using targeted assays. (2) Results: BAL macrophages from 18 COPD and 10 (non-COPD) control subjects were evaluated. The majority of macrophages from COPD subjects were non-polarized (negative for both M1 and M2 markers; 77.9%) in contrast to controls (23.9%; <i>p </i>< 0.001). The percentages of these non-polarized macrophages strongly correlated with the severity of COPD (<i>p </i>= 0.006) and current smoking status (<i>p </i>= 0.008). Non-polarized macrophages demonstrated poor phagocytic function in both the control (<i>p </i>= 0.02) and COPD (<i>p</i> < 0.001) subjects. Non-polarized macrophages demonstrated impaired ability to phagocytose <i>Staphylococcus aureus </i>(<i>p </i>< 0.001). They also demonstrated reduced gene expression for CD163, CD40, CCL13 and C1QA&B, which are involved in pathogen recognition and processing and showed an increased gene expression for CXCR4, RAF1, amphiregulin and MAP3K5, which are all involved in promoting the inflammatory response. (3) Conclusions: COPD is associated with an abundance of non-polarized airway macrophages that is related to the severity of COPD. These non-polarized macrophages are predominantly responsible for the poor phagocytic capacity of lung macrophages in COPD, having reduced capacity for pathogen recognition and processing. This could be a key risk factor for COPD exacerbation and could contribute to disease progression. |
topic |
macrophages phagocytosis COPD phenotype inflammation |
url |
https://www.mdpi.com/2227-9059/8/10/398 |
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doaj-0535300b8f744d43a4afde119a7d7c2d2020-11-25T03:56:15ZengMDPI AGBiomedicines2227-90592020-10-01839839810.3390/biomedicines8100398Abundance of Non-Polarized Lung Macrophages with Poor Phagocytic Function in Chronic Obstructive Pulmonary Disease (COPD)Kentaro Akata0Kei Yamasaki1Fernando Sergio Leitao Filho2Chen Xi Yang3Hiroto Takiguchi4Basak Sahin5Beth A Whalen6Cheng Wei Tony Yang7Janice M Leung8Don D Sin9Stephanus van Eeden10Department of Respiratory Medicine, University of Occupational and Environmental Health Japan, Fukuoka 807-8555, JapanDepartment of Respiratory Medicine, University of Occupational and Environmental Health Japan, Fukuoka 807-8555, JapanDepartment of Medicine (Respirology), University of British Columbia, Centre for Heart Lung Innovation, St. Paul’s Hospital, Vancouver, BC V6Z1Y6, CanadaDepartment of Medicine (Respirology), University of British Columbia, Centre for Heart Lung Innovation, St. Paul’s Hospital, Vancouver, BC V6Z1Y6, CanadaDepartment of Medicine (Respirology), University of British Columbia, Centre for Heart Lung Innovation, St. Paul’s Hospital, Vancouver, BC V6Z1Y6, CanadaDepartment of Medicine (Respirology), University of British Columbia, Centre for Heart Lung Innovation, St. Paul’s Hospital, Vancouver, BC V6Z1Y6, CanadaDepartment of Medicine (Respirology), University of British Columbia, Centre for Heart Lung Innovation, St. Paul’s Hospital, Vancouver, BC V6Z1Y6, CanadaDepartment of Medicine (Respirology), University of British Columbia, Centre for Heart Lung Innovation, St. Paul’s Hospital, Vancouver, BC V6Z1Y6, CanadaDepartment of Medicine (Respirology), University of British Columbia, Centre for Heart Lung Innovation, St. Paul’s Hospital, Vancouver, BC V6Z1Y6, CanadaDepartment of Medicine (Respirology), University of British Columbia, Centre for Heart Lung Innovation, St. Paul’s Hospital, Vancouver, BC V6Z1Y6, CanadaDepartment of Medicine (Respirology), University of British Columbia, Centre for Heart Lung Innovation, St. Paul’s Hospital, Vancouver, BC V6Z1Y6, CanadaLung macrophages are the key immune effector cells in the pathogenesis of Chronic Obstructive Pulmonary Disease (COPD). Several studies have shown an increase in their numbers in bronchoalveolar lavage fluid (BAL) of subjects with COPD compared to controls, suggesting a pathogenic role in disease initiation and progression. Although reduced lung macrophage phagocytic ability has been previously shown in COPD, the relationship between lung macrophages’ phenotypic characteristics and functional properties in COPD is still unclear. (1) Methods: Macrophages harvested from bronchoalveolar lavage (BAL) fluid of subjects with and without COPD (GOLD grades, I–III) were immuno-phenotyped, and their function and gene expression profiles were assessed using targeted assays. (2) Results: BAL macrophages from 18 COPD and 10 (non-COPD) control subjects were evaluated. The majority of macrophages from COPD subjects were non-polarized (negative for both M1 and M2 markers; 77.9%) in contrast to controls (23.9%; <i>p </i>< 0.001). The percentages of these non-polarized macrophages strongly correlated with the severity of COPD (<i>p </i>= 0.006) and current smoking status (<i>p </i>= 0.008). Non-polarized macrophages demonstrated poor phagocytic function in both the control (<i>p </i>= 0.02) and COPD (<i>p</i> < 0.001) subjects. Non-polarized macrophages demonstrated impaired ability to phagocytose <i>Staphylococcus aureus </i>(<i>p </i>< 0.001). They also demonstrated reduced gene expression for CD163, CD40, CCL13 and C1QA&B, which are involved in pathogen recognition and processing and showed an increased gene expression for CXCR4, RAF1, amphiregulin and MAP3K5, which are all involved in promoting the inflammatory response. (3) Conclusions: COPD is associated with an abundance of non-polarized airway macrophages that is related to the severity of COPD. These non-polarized macrophages are predominantly responsible for the poor phagocytic capacity of lung macrophages in COPD, having reduced capacity for pathogen recognition and processing. This could be a key risk factor for COPD exacerbation and could contribute to disease progression.https://www.mdpi.com/2227-9059/8/10/398macrophagesphagocytosisCOPDphenotypeinflammation |