COPD monocytes demonstrate impaired migratory ability

• Published in: Respiratory research Vol. 18; no. 1; p. 90
• Main Authors: Ravi, Arjun K, Plumb, Jonathan, Gaskell, Rosemary, Mason, Sarah, Broome, Caroline S, Booth, George, Catley, Matthew, Vestbo, Jørgen, Singh, Dave
• Format: Journal Article
• Language: English
• Published: England BioMed Central 11-05-2017; BMC
• Subjects: Aged; Alveoli; Apoptosis; Blood; CCR5; CCR5 protein; CD14 antigen; CD16 antigen; Cell Movement - immunology; Cells, Cultured; Chemokines; Chemotaxis; Chronic obstructive pulmonary disease; COPD; Cytokines; Cytometry; Dendritic cells; Experiments; Female; Flow cytometry; Gene expression; Humans; Immunoassay; Immunohistochemistry; Inflammation; Interleukin 6; Interleukin 6 receptors; Interleukin-6 - blood; Interleukin-6 - immunology; Interleukins; Leukocyte migration; Ligands; Lung diseases; Lungs; Macrophages; Male; Middle Aged; Monocytes; Monocytes - immunology; Monocytes - pathology; Patients; Plasma; Polymerase chain reaction; Pulmonary Disease, Chronic Obstructive - blood; Pulmonary Disease, Chronic Obstructive - immunology; Pulmonary Disease, Chronic Obstructive - pathology; Receptors, CCR5 - blood; Receptors, CCR5 - immunology; Replication; Rheumatoid arthritis; Sampling; Signaling; Smoking; Sputum; Stimulation; Studies; Young Adult; Monocytes; CCR5; Chemotaxis; COPD; Interleukin-6
• DOI: 10.1186/s12931-017-0569-y
• EISSN: 1465-993X; 1465-9921

Increased lung macrophage numbers in COPD may arise from upregulation of blood monocyte recruitment into the lungs. CCR5 is a monocyte chemokine receptor regulated by interleukin-6 (IL-6); the concentration of CCR5 ligands are known to be elevated in COPD lungs. The objective of this study was to investigate mechanisms of monocyte recruitment to the lung in COPD, including the role of CCR5 signalling.
Ninety one COPD patients, 29 smokers (S) and 37 non-smokers (NS) underwent sputum induction, plasma sampling (to measure IL-6 and soluble IL-6 receptor [sIL-6R] by immunoassay), monocyte characterization (by flow cytometry) and monocyte isolation for cell migration and quantitative polymerase chain reaction studies. Lung tissue was used for immunohistochemistry.
Plasma IL-6 and sIL-6R levels were increased in COPD. Greater proportions of COPD CD14
CD16
monocytes expressed CCR5 compared to controls. Monocyte stimulation with IL-6 and sIL-6R increased CCR5 gene expression. COPD monocytes demonstrated impaired migration towards sputum supernatant compared to NS (% migration, 4.4 vs 11.5, respectively; p < 0.05). Pulmonary microvessels showed reduced monocyte recruitment (% marginated cells) in COPD compared to NS, (9.3% vs 83.1%, respectively). The proportion of replicating Ki67
alveolar macrophages was reduced in COPD compared to NS. All alveolar macrophages from COPD and S expressed the anti-apoptosis marker BCL2; this protein was not present in non-smokers or COPD ex-smokers.
COPD monocytes show decreased migratory ability despite increased CCR5 expression. Increased COPD lung macrophage numbers may be due to delayed apoptosis.