The Emerging Role of Macrophages in Chronic Obstructive Pulmonary Disease: The Potential Impact of Oxidative Stress and Extracellular Vesicle on Macrophage Polarization and Function

Overview

Journal Antioxidants (Basel)

Date 2022 Mar 25

PMID 35326114

Authors

Mauro Finicelli

Filomena Anna Digilio

Umberto Galderisi

Gianfranco Peluso

Affiliations

Soon will be listed here.

Abstract

Chronic obstructive pulmonary disease (COPD) is one of the most common airway diseases, and it is considered a major global health problem. Macrophages are the most representative immune cells in the respiratory tract, given their role in surveying airways, removing cellular debris, immune surveillance, and resolving inflammation. Macrophages exert their functions by adopting phenotypical changes based on the stimuli they receive from the surrounding tissue. This plasticity is described as M1/M2 macrophage polarization, which consists of a strictly coordinated process leading to a difference in the expression of surface markers, the production of specific factors, and the execution of biological activities. This review focuses on the role played by macrophages in COPD and their implication in inflammatory and oxidative stress processes. Particular attention is on macrophage polarization, given macrophage plasticity is a key feature in COPD. We also discuss the regulatory influence of extracellular vesicles (EVs) in cell-to-cell communications. EV composition and cargo may influence many COPD-related aspects, including inflammation, tissue remodeling, and macrophage dysfunctions. These findings could be useful for better addressing the role of macrophages in the complex pathogenesis and outcomes of COPD.

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References

Kirkham P, Barnes P . Oxidative stress in COPD. Chest. 2013; 144(1):266-273. DOI: 10.1378/chest.12-2664. View

Li M, Yu D, Williams K, Liu M . Tobacco smoke induces the generation of procoagulant microvesicles from human monocytes/macrophages. Arterioscler Thromb Vasc Biol. 2010; 30(9):1818-24. PMC: 2939448. DOI: 10.1161/ATVBAHA.110.209577. View

Le Y, Cao W, Zhou L, Fan X, Liu Q, Liu F . Infection of Promotes Both M1/M2 Polarization and MMP Production in Cigarette Smoke-Exposed Macrophages. Front Immunol. 2020; 11:1902. PMC: 7468417. DOI: 10.3389/fimmu.2020.01902. View

Kim Y, Ahn J, Kim S, Kim H, Kim S, Kang J . The potential theragnostic (diagnostic+therapeutic) application of exosomes in diverse biomedical fields. Korean J Physiol Pharmacol. 2018; 22(2):113-125. PMC: 5840070. DOI: 10.4196/kjpp.2018.22.2.113. View

Keatings V, Collins P, Scott D, Barnes P . Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma. Am J Respir Crit Care Med. 1996; 153(2):530-4. DOI: 10.1164/ajrccm.153.2.8564092. View

Russell D, Genschmer K, Blalock J . Extracellular Vesicles as Central Mediators of COPD Pathophysiology. Annu Rev Physiol. 2021; 84:631-654. PMC: 8831481. DOI: 10.1146/annurev-physiol-061121-035838. View

Sun X, Liu Y, Feng X, Li C, Li S, Zhao Z . The key role of macrophage depolarization in the treatment of COPD with ergosterol both in vitro and in vivo. Int Immunopharmacol. 2019; 79:106086. DOI: 10.1016/j.intimp.2019.106086. View

Facchinetti F, Amadei F, Geppetti P, Tarantini F, Di Serio C, Dragotto A . Alpha,beta-unsaturated aldehydes in cigarette smoke release inflammatory mediators from human macrophages. Am J Respir Cell Mol Biol. 2007; 37(5):617-23. DOI: 10.1165/rcmb.2007-0130OC. View

Berenson C, Kruzel R, Wrona C, Mammen M, Sethi S . Impaired Innate COPD Alveolar Macrophage Responses and Toll-Like Receptor-9 Polymorphisms. PLoS One. 2015; 10(9):e0134209. PMC: 4567310. DOI: 10.1371/journal.pone.0134209. View

10.

Eapen M, Hansbro P, McAlinden K, Kim R, Ward C, Hackett T . Abnormal M1/M2 macrophage phenotype profiles in the small airway wall and lumen in smokers and chronic obstructive pulmonary disease (COPD). Sci Rep. 2017; 7(1):13392. PMC: 5645352. DOI: 10.1038/s41598-017-13888-x. View

11.

Trappe A, Donnelly S, McNally P, Coppinger J . Role of extracellular vesicles in chronic lung disease. Thorax. 2021; 76(10):1047-1056. PMC: 8461402. DOI: 10.1136/thoraxjnl-2020-216370. View

12.

Mears R, Craven R, Hanrahan S, Totty N, Upton C, Young S . Proteomic analysis of melanoma-derived exosomes by two-dimensional polyacrylamide gel electrophoresis and mass spectrometry. Proteomics. 2004; 4(12):4019-31. DOI: 10.1002/pmic.200400876. View

13.

Jubrail J, Kurian N, Niedergang F . Macrophage phagocytosis cracking the defect code in COPD. Biomed J. 2018; 40(6):305-312. PMC: 6138611. DOI: 10.1016/j.bj.2017.09.004. View

14.

Singh R, Belchamber K, Fenwick P, Chana K, Donaldson G, Wedzicha J . Defective monocyte-derived macrophage phagocytosis is associated with exacerbation frequency in COPD. Respir Res. 2021; 22(1):113. PMC: 8059282. DOI: 10.1186/s12931-021-01718-8. View

15.

Russell R, Culpitt S, DeMatos C, Donnelly L, Smith M, Wiggins J . Release and activity of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 by alveolar macrophages from patients with chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol. 2002; 26(5):602-9. DOI: 10.1165/ajrcmb.26.5.4685. View

16.

Zaynagetdinov R, Sherrill T, Gleaves L, Hunt P, Han W, McLoed A . Chronic NF-κB activation links COPD and lung cancer through generation of an immunosuppressive microenvironment in the lungs. Oncotarget. 2016; 7(5):5470-82. PMC: 4868699. DOI: 10.18632/oncotarget.6562. View

17.

Wang L, Chen Q, Yu Q, Xiao J, Zhao H . Cigarette smoke extract-treated airway epithelial cells-derived exosomes promote M1 macrophage polarization in chronic obstructive pulmonary disease. Int Immunopharmacol. 2021; 96:107700. DOI: 10.1016/j.intimp.2021.107700. View

18.

Akata K, van Eeden S . Lung Macrophage Functional Properties in Chronic Obstructive Pulmonary Disease. Int J Mol Sci. 2020; 21(3). PMC: 7037150. DOI: 10.3390/ijms21030853. View

19.

Barnes P, Burney P, Silverman E, Celli B, Vestbo J, Wedzicha J . Chronic obstructive pulmonary disease. Nat Rev Dis Primers. 2016; 1:15076. DOI: 10.1038/nrdp.2015.76. View

20.

Caramori G, Adcock I, Casolari P, Ito K, Jazrawi E, Tsaprouni L . Unbalanced oxidant-induced DNA damage and repair in COPD: a link towards lung cancer. Thorax. 2011; 66(6):521-7. DOI: 10.1136/thx.2010.156448. View