Defective bacterial phagocytosis is associated with dysfunctional mitochondria in COPD macrophages

COPD-MAP consortium; Kylie B.R. Belchamber; Richa Singh; Craig M. Batista; Moira K. Whyte; David H. Dockrell; Iain Kilty; Jadwiga A. Wedzicha; Matthew J. Robinson; Peter J. Barnes; Louise E. Donnelly

Defective bacterial phagocytosis is associated with dysfunctional mitochondria in COPD macrophages

COPD-MAP consortium, Kylie B.R. Belchamber, Richa Singh, Craig M. Batista, Moira K. Whyte, David H. Dockrell, Iain Kilty, Jadwiga A. Wedzicha, Matthew J. Robinson, Peter J. Barnes, Louise E. Donnelly

Division of Developmental Biology & Medicine (L5)

Granta Park

Research output: Contribution to journal › Article › peer-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 language	English
Article number	1802244
Pages (from-to)	1-14
Number of pages	14
Journal	European Respiratory Journal
Volume	54
Issue number	4
Publication status	Published - 1 Oct 2019

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

https://erj.ersjournals.com/content/54/4/1802244

Cite this

COPD-MAP consortium, Belchamber, K. B. R., Singh, R., Batista, C. M., Whyte, M. K., Dockrell, D. H., Kilty, I., Wedzicha, J. A., Robinson, M. J., Barnes, P. J., & Donnelly, L. E. (2019). Defective bacterial phagocytosis is associated with dysfunctional mitochondria in COPD macrophages. European Respiratory Journal, 54(4), 1-14. Article 1802244. https://erj.ersjournals.com/content/54/4/1802244

@article{127a1b95f824493db6249757908ff233,

title = "Defective bacterial phagocytosis is associated with dysfunctional mitochondria in COPD macrophages",

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.",

author = "{COPD-MAP consortium} and Belchamber, {Kylie B.R.} and Richa Singh and Batista, {Craig M.} and Whyte, {Moira K.} and Dockrell, {David H.} and Iain Kilty and Wedzicha, {Jadwiga A.} and Robinson, {Matthew J.} and Barnes, {Peter J.} and Donnelly, {Louise E.}",

year = "2019",

month = oct,

day = "1",

language = "English",

volume = "54",

pages = "1--14",

journal = "European Respiratory Journal",

issn = "0903-1936",

publisher = "European Respiratory Society",

number = "4",

}

COPD-MAP consortium, Belchamber, KBR, Singh, R, Batista, CM, Whyte, MK, Dockrell, DH, Kilty, I, Wedzicha, JA, Robinson, MJ, Barnes, PJ & Donnelly, LE 2019, 'Defective bacterial phagocytosis is associated with dysfunctional mitochondria in COPD macrophages', European Respiratory Journal, vol. 54, no. 4, 1802244, pp. 1-14. <https://erj.ersjournals.com/content/54/4/1802244>

TY - JOUR

T1 - Defective bacterial phagocytosis is associated with dysfunctional mitochondria in COPD macrophages

AU - COPD-MAP consortium

AU - Belchamber, Kylie B.R.

AU - Singh, Richa

AU - Batista, Craig M.

AU - Whyte, Moira K.

AU - Dockrell, David H.

AU - Kilty, Iain

AU - Wedzicha, Jadwiga A.

AU - Robinson, Matthew J.

AU - Barnes, Peter J.

AU - Donnelly, Louise E.

PY - 2019/10/1

Y1 - 2019/10/1

N2 - 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.

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-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.

M3 - Article

SN - 0903-1936

VL - 54

SP - 1

EP - 14

JO - European Respiratory Journal

JF - European Respiratory Journal

IS - 4

M1 - 1802244

ER -

Defective bacterial phagocytosis is associated with dysfunctional mitochondria in COPD macrophages

Abstract

UN SDGs

Access to Document

Fingerprint

Cite this