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Respiratory Research
Published in: Respiratory Research 1/2017

Open Access 01-12-2017 | Research

COPD monocytes demonstrate impaired migratory ability

Authors: Arjun K Ravi, Jonathan Plumb, Rosemary Gaskell, Sarah Mason, Caroline S Broome, George Booth, Matthew Catley, Jørgen Vestbo, Dave Singh

Published in: Respiratory Research | Issue 1/2017

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

COPD monocytes show decreased migratory ability despite increased CCR5 expression. Increased COPD lung macrophage numbers may be due to delayed apoptosis.
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Metadata
Title
COPD monocytes demonstrate impaired migratory ability
Authors
Arjun K Ravi
Jonathan Plumb
Rosemary Gaskell
Sarah Mason
Caroline S Broome
George Booth
Matthew Catley
Jørgen Vestbo
Dave Singh
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2017
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-017-0569-y

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