Imperial College London
Alternate

ProfessorLouiseDonnelly

Faculty of Medicine, National Heart & Lung Institute

Professor of Respiratory Cell Biology
 
 
 
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Contact

 

+44 (0)20 7594 7895l.donnelly

 
 
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Location

 

419Guy Scadding BuildingRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Belchamber:2019:10.1183/13993003.02244-2018,
author = {Belchamber, K and Singh, R and Batista, C and Moira, W and Dockrell, D and Kilty, I and Matthew, R and Wedzicha, J and Barnes, P and Donnelly, L},
doi = {10.1183/13993003.02244-2018},
journal = {European Respiratory Journal},
pages = {1--14},
title = {Defective bacterial phagocytosis is associated with dysfunctional mitochondria in COPD macrophages},
url = {http://dx.doi.org/10.1183/13993003.02244-2018},
volume = {54},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background: Increased reactive oxygen species (ROS) have been implicated in the pathophysiology of chronic obstructive pulmonary disease (COPD). Objective: This study examined the effect of exogenous and endogenous oxidative stress on macrophage phagocytosis in patients with COPD. Methods: Monocyte-derived macrophages (MDM) were generated from non-smoker, smoker and COPD subjects, differentiated in either GM-CSF (G-M) or M-CSF (M-M). Alveolar macrophages were isolated from lung tissue or bronchoalveolar lavage. Macrophages were incubated +/- 200M H2O2 for 24 hours, then exposed to fluorescently-labelled H. influenzae or S. pneumoniae for 4 hours, after which phagocytosis, mitochondrial ROS (mROS), and mitochondrial membrane potential (m) were measured. Results: Phagocytosis of bacteria was significantly decreased in both G-M and M-M from  COPD patients, compared to non-smoker controls. In non-smokers and smokers, bacterial phagocytosis did not alter mROS or m, however in COPD, phagocytosis increased early mROS and decreased m in both G-M and M-M. Exogenous oxidative stress reduced phagocytosis in non-smoker and COPD alveolar macrophages, and non-smoker MDM, associated with reduced mROS production. Conclusion: COPD macrophages show defective phagocytosis, which is associated with altered mitochondrial  function and an inability to regulate mROS production. Targeting mitochondrial dysfunction may restore the phagocytic defect in COPD.
AU  - Belchamber,K
AU  - Singh,R
AU  - Batista,C
AU  - Moira,W
AU  - Dockrell,D
AU  - Kilty,I
AU  - Matthew,R
AU  - Wedzicha,J
AU  - Barnes,P
AU  - Donnelly,L
DO  - 10.1183/13993003.02244-2018
EP  - 14
PY  - 2019///
SN  - 0903-1936
SP  - 1
TI  - Defective bacterial phagocytosis is associated with dysfunctional mitochondria in COPD macrophages
T2  - European Respiratory Journal
UR  - http://dx.doi.org/10.1183/13993003.02244-2018
UR  - https://erj.ersjournals.com/content/54/4/1802244
UR  - http://hdl.handle.net/10044/1/71737
VL  - 54
ER  -
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