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Rights statement: Author's peer reviewed manuscript as accepted for publication.
Accepted author manuscript, 738 KB, PDF document
Original language | English |
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Journal | European Respiratory Journal |
Volume | 54 |
Issue number | 4 |
Early online date | 10 Oct 2019 |
DOIs | |
Publication status | E-pub ahead of print - 10 Oct 2019 |
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-Mϕ) or M-CSF (M-Mϕ). Alveolar macrophages were isolated from lung tissue or bronchoalveolar lavage. Macrophages were incubated +/- 200 µM H2O2 for 24 h, then exposed to fluorescently-labelled H. influenzae or S. pneumoniae for 4 h, after which phagocytosis, mitochondrial ROS (mROS), and mitochondrial membrane potential (ΔΨm) were measured.
RESULTS: Phagocytosis of bacteria was significantly decreased in both G-Mϕ and M-Mϕ from COPD patients, compared to non-smoker controls. In non-smokers and smokers, bacterial phagocytosis did not alter mROS or ΔΨm, however in COPD, phagocytosis increased early mROS and decreased ΔΨm in both G-Mϕ and M-Mϕ. 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.
ID: 113137329