Defective bacterial phagocytosis is associated with dysfunctional mitochondria in COPD macrophages

COPDMAP consortium

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
JournalEuropean Respiratory Journal
Volume54
Issue number4
Early online date10 Oct 2019
DOIs
Publication statusE-pub ahead of print - 10 Oct 2019

Fingerprint

Dive into the research topics of 'Defective bacterial phagocytosis is associated with dysfunctional mitochondria in COPD macrophages'. Together they form a unique fingerprint.

Cite this