Defective monocyte-derived macrophage phagocytosis is associated with exacerbation frequency in COPD

• Published in: Respiratory research Vol. 22; no. 1; p. 113
• Main Authors: Singh, R, Belchamber, K B R, Fenwick, P S, Chana, K, Donaldson, G, Wedzicha, J A, Barnes, P J, Donnelly, L E
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 20-04-2021; BioMed Central; BMC
• Subjects: Aged; Airway management; Bacteria; Bacterial infections; Bronchodilators; Case-Control Studies; Cells, Cultured; Chronic obstructive pulmonary disease; Colonization; Complications and side effects; COPD; Corticoids; Corticosteroids; Cytokines; Demographics; Development and progression; Disease Progression; Exacerbation; Female; Fluorimetry; Genotype & phenotype; Haemophilus influenzae - immunology; Haemophilus influenzae - pathogenicity; Health aspects; Humans; Inflammation; Inflammation Mediators - metabolism; Interleukin-8 - metabolism; Lower airway bacterial colonisation; Lung - immunology; Lung - metabolism; Lung - microbiology; Lung diseases, Obstructive; Lungs; Macrophage; Macrophages; Macrophages - immunology; Macrophages - metabolism; Macrophages - microbiology; Male; Monocytes; Patients; Phagocytosis; Phenotype; Physiological aspects; Pulmonary Disease, Chronic Obstructive - diagnosis; Pulmonary Disease, Chronic Obstructive - immunology; Pulmonary Disease, Chronic Obstructive - metabolism; Pulmonary Disease, Chronic Obstructive - microbiology; Respiratory function; Sputum; Streptococcus infections; Streptococcus pneumoniae; Streptococcus pneumoniae - immunology; Streptococcus pneumoniae - pathogenicity; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α; United Kingdom; Exacerbation; Lower airway bacterial colonisation; COPD; Macrophage
• ISSN: 1465-993X; 1465-9921; 1465-993X; 1465-9921
• DOI: 10.1186/s12931-021-01718-8

Lower airway bacterial colonisation (LABC) in COPD patients is associated with increased exacerbation frequency and faster lung function decline. Defective macrophage phagocytosis in COPD drives inflammation, but how defective macrophage function contributes to exacerbations is not clear. This study investigated the association between macrophage phagocytosis and exacerbation frequency, LABC and clinical parameters.
Monocyte-derived macrophages (MDM) were generated from 92 stable COPD patients, and at the onset of exacerbation in 39 patients. Macrophages were exposed to fluorescently labelled Haemophilus influenzae or Streptococcus pneumoniae for 4 h, then phagocytosis measured by fluorimetry and cytokine release by ELISA. Sputum bacterial colonisation was measured by PCR.
Phagocytosis of H. influenzae was negatively correlated with exacerbation frequency (r = 0.440, p < 0.01), and was significantly reduced in frequent vs. infrequent exacerbators (1.9 × 10
RFU vs. 2.5 × 10
RFU, p < 0.01). There was no correlation for S. pneumoniae. There was no association between phagocytosis of either bacteria with age, lung function, smoking history or treatment with inhaled corticosteroids, or long-acting bronchodilators. Phagocytosis was not altered during an exacerbation, or in the 2 weeks post-exacerbation. In response to phagocytosis, MDM from exacerbating patients showed increased release of CXCL-8 (p < 0.001) and TNFα (p < 0.01) compared to stable state.
Impaired COPD macrophage phagocytosis of H. influenzae, but not S. pneumoniae is associated with exacerbation frequency, resulting in pro-inflammatory macrophages that may contribute to disease progression. Targeting these frequent exacerbators with drugs that improve macrophage phagocytosis may prove beneficial.