COPD monocytes demonstrate impaired migratory ability

Respiratory Research

Research

George Booth¹  Sarah Mason¹  Jørgen Vestbo¹  Jonathan Plumb¹  Rosemary Gaskell¹  Caroline S Broome²  Dave Singh²  Arjun K Ravi²  Matthew Catley³ 

[1] NIHR Respiratory and Allergy Clinical Research Facility, Manchester Academic Health Science Centre, University Hospital South Manchester NHS Foundation Trust, University of Manchester, Manchester, UK;NIHR Respiratory and Allergy Clinical Research Facility, Manchester Academic Health Science Centre, University Hospital South Manchester NHS Foundation Trust, University of Manchester, Manchester, UK;The Medicines Evaluation Unit, Wythenshawe Hospital, The Langley Building, Southmoor Road, M23 9QZ, Wythenshawe, Greater Manchester, UK;UCB, Slough, Berkshire, UK;

关键词: COPD;    Monocytes;    CCR5;    Chemotaxis;    Interleukin-6;   

DOI  :  10.1186/s12931-017-0569-y

 received in 2016-11-21, accepted in 2017-05-01,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundIncreased 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.MethodsNinety 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.ResultsPlasma 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.ConclusionCOPD monocytes show decreased migratory ability despite increased CCR5 expression. Increased COPD lung macrophage numbers may be due to delayed apoptosis.

【 授权许可】

CC BY   
© The Author(s). 2017