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Published on: October 22, 2019
Abundance of Non-Polarized Lung Macrophages with Poor Phagocytic Function in Chronic Obstructive Pulmonary Disease
Kentaro Akata1, Kei Yamasaki1, Fernando Sergio Leitao Filho2
1Department of Respiratory Medicine, University of Occupational and Environmental Health Japan, Fukuoka 807-8555, Japan.
Abstract:
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%; p < 0.001). The percentages of these non-polarized macrophages strongly correlated with the severity of COPD (p = 0.006) and current smoking status (p = 0.008). Non-polarized macrophages demonstrated poor phagocytic function in both the control (p = 0.02) and COPD (p < 0.001) subjects. Non-polarized macrophages demonstrated impaired ability to phagocytose Staphylococcus aureus (p < 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.
Insights
Chronic Obstructive Pulmonary Disease (COPD) is linked to an increase in non-polarized lung macrophages. These macrophages exhibit poor phagocytic function, contributing to disease severity and potential exacerbations.
Area of Science:
- Immunology
- Pulmonology
- Cell Biology
Background:
- Lung macrophages are crucial in Chronic Obstructive Pulmonary Disease (COPD) pathogenesis.
- Increased macrophage numbers in COPD bronchoalveolar lavage fluid (BAL) suggest a pathogenic role.
- The link between lung macrophage phenotype and function in COPD remains unclear.
Purpose of the Study:
- To investigate the phenotypic characteristics and functional properties of lung macrophages in COPD patients.
- To determine the relationship between macrophage polarization and disease severity in COPD.
- To assess the phagocytic capacity and gene expression profiles of COPD lung macrophages.
Main Methods:
- Macrophages were isolated from BAL fluid of COPD (GOLD grades I-III) and control subjects.
- Immuno-phenotyping, functional assays, and targeted gene expression analysis were performed.
- Analysis included 18 COPD patients and 10 non-COPD controls.
Main Results:
- COPD subjects had a significantly higher percentage of non-polarized macrophages (77.9%) compared to controls (23.9%).
- Non-polarized macrophage abundance correlated with COPD severity and smoking status.
- These macrophages exhibited impaired phagocytosis of Staphylococcus aureus and altered gene expression related to pathogen processing and inflammation.
Conclusions:
- COPD is characterized by an abundance of non-polarized airway macrophages, associated with disease severity.
- Non-polarized macrophages are responsible for the reduced phagocytic capacity observed in COPD lung macrophages.
- This impaired immune function may increase the risk of COPD exacerbations and contribute to disease progression.
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