Imperial College London
Alternate

RESEARCH TECHNICIAN

Faculty of Medicine, National Heart & Lung Institute

Research Technician
 
 
 
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Contact

 

+44 (0)20 7594 7897p.fenwick

 
 
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Location

 

Technician Room 229BGuy Scadding BuildingRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Singh:2021:10.1186/s12931-021-01718-8,
author = {Singh, R and Belchamber, K and Fenwick, P and Chana, K and Donaldson, G and Wedzicha, J and Barnes, P and Donnelly, L},
doi = {10.1186/s12931-021-01718-8},
journal = {Respiratory Research},
pages = {1--11},
title = {Defective monocyte-derived macrophage phagocytosis is associated with exacerbation frequency in COPD},
url = {http://dx.doi.org/10.1186/s12931-021-01718-8},
volume = {22},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundLower 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.MethodsMonocyte-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.ResultsPhagocytosis 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 × 103 RFU vs. 2.5 × 103 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.ConclusionImpaired 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.
AU  - Singh,R
AU  - Belchamber,K
AU  - Fenwick,P
AU  - Chana,K
AU  - Donaldson,G
AU  - Wedzicha,J
AU  - Barnes,P
AU  - Donnelly,L
DO  - 10.1186/s12931-021-01718-8
EP  - 11
PY  - 2021///
SN  - 1465-9921
SP  - 1
TI  - Defective monocyte-derived macrophage phagocytosis is associated with exacerbation frequency in COPD
T2  - Respiratory Research
UR  - http://dx.doi.org/10.1186/s12931-021-01718-8
UR  - https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-021-01718-8
UR  - http://hdl.handle.net/10044/1/89477
VL  - 22
ER  -
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