Macrophage Polarization and Functions in Pathogenesis of Chronic Obstructive Pulmonary Disease
Abstract
:1. Introduction
2. Pathophysiology of COPD
2.1. Airflow Limitation
2.2. Small Airway Obstruction
2.3. Emphysema
2.4. Chronic Bronchitis
2.5. Airway Mucus Hyperproduction
2.6. Impairment of Gas Exchange
3. Etiology of COPD
3.1. Oxidative Stress
3.2. Protease–Antiprotease Imbalance
3.3. Inflammatory Mediators
3.4. Inflammatory Cells
4. Macrophages and Their Polarization
5. Pulmonary Macrophage
6. Role of Macrophages and Their Polarization in COPD
7. Altered Function of Macrophage in Patients with COPD
7.1. Altered Macrophage Phenotype
7.2. Impaired Phagocytic Activity
7.3. Inflammatory Response
7.4. Lipid-Laden Foamy Macrophages
8. Macrophage-Targeting COPD Treatment
8.1. Regulation of Macrophage Phenotype
8.2. Enhanced Phagocytic Activity
8.3. Reduced Inflammatory Response
8.4. Reduced Lipid-Laden Foamy Macrophages
Therapeutic Means | Target and Mechanisms | Effect on Macrophage Function | Ref. |
---|---|---|---|
Plant compound (Salidroside) | JNK/c-Jun | Inhibited M1 polarization of alveolar macrophages in lung tissues of CS-induced pulmonary inflammation rat model and alveolar macrophage from BALF | [182] |
Mycosterol (Ergosterol) | HDAC3 | Inhibited M1 polarization and increased M2 polarization in CSE-induced COPD rat model and raw cells Elevated HDAC3 activation and suppressed HAT activity and NFκB/p65 acetylation | [184] |
Thiazolidinedione compound (Rosiglitazone) | PPARγ and RXRα | Inhibited M1 polarization in lung and BALF of CS-induced COPD model and alveolar macrophage from BALF | [185] |
PPARγ agonist | JAK-STAT, MAPK and NFκB | Inhibited M1 polarization and increased M2 polarization in CS-induced COPD mice | [152] |
Plant compound (ECC) | mTORC2 | Inhibited M2 macrophage polarization by inhibition of mTORC2 activity in IL4-induced polarization in MH-S cells | [191] |
Macrolide antibiotics (Azithromycin) | Increased phagocytosis of E. coli and efferocytosis | [162,192] | |
Nonantibiotic macrolides (GS-459755, GS-560660) | NLRP3 | Increased phagocytosis of NTHI and efferocytosis Decreased the NLRP3 and IL1β in THP-1 cells | [193] |
Corticosteroid (Dexamethasone) | Increased efferocytosis | [194] | |
S1PR3 and S1PR5 agonist (Suramin) | Increased efferocytosis | [165] | |
Plant compound (Sulforaphane) | NRF2 | Increased phagocytosis of NTHI and P. aeruginosa by increasing MARCO | [197] |
PDE4 inhibitor (Roflumilast) | Increased phagocytosis | [195] | |
PDE4 inhibitor (CHF6001 and roflumilast) | CREB | Inhibited TNFα stimulated with LPS in alveolar macrophage and lung tissues of patients with COPD | [199] |
Exogenous SP-D | NRF2 | Decreased lipid-laden macrophages Improved lung function and attenuated airway inflammation in ozone-exposed mice | [179] |
miR-103a | Decreased lipid-laden macrophages | [202] |
9. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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M1 | M2 | DP | DN | Source | Method | Ref | |
---|---|---|---|---|---|---|---|
Marker | CD40+CD163− | CD40−CD163+ | CD40+CD163+ | CD40−CD163− | BALF | Flow cytometry | [155] |
COPD (vs. NC) | NS | NS | Decreased | Increased | |||
Marker | CD40+CD163− | CD40−CD163+ | CD40+CD163+ | CD40−CD163− | BALF | Flow cytometry | [137] |
COPD (vs. NC) | NS | NS | Decreased | Increased | |||
Marker | CD86+ | CD206+ | BALF | Flow cytometry | [152] | ||
COPD (vs. NC) | Increased | Increased | No detection | No detection | |||
Marker | iNOS+ | CD206+ | Lung tissues | IHC | [149,156] | ||
COPD (vs. NC) | Decreased | Increased | No detection | No detection | |||
Marker | iNOS+ | CD206+ | iNOS+CD206+ | iNOS−CD206− | Lung tissues | IHC | [157] |
COPD (vs. NC) | Increased | Increased | Increased | Decreased | |||
Marker | CD163+, CD204+, or CD206+ | Lung tissues | IHC | [158] | |||
COPD (vs. NC) | No detect | Increased | No detection | No detection |
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Kim, G.-D.; Lim, E.Y.; Shin, H.S. Macrophage Polarization and Functions in Pathogenesis of Chronic Obstructive Pulmonary Disease. Int. J. Mol. Sci. 2024, 25, 5631. https://doi.org/10.3390/ijms25115631
Kim G-D, Lim EY, Shin HS. Macrophage Polarization and Functions in Pathogenesis of Chronic Obstructive Pulmonary Disease. International Journal of Molecular Sciences. 2024; 25(11):5631. https://doi.org/10.3390/ijms25115631
Chicago/Turabian StyleKim, Gun-Dong, Eun Yeong Lim, and Hee Soon Shin. 2024. "Macrophage Polarization and Functions in Pathogenesis of Chronic Obstructive Pulmonary Disease" International Journal of Molecular Sciences 25, no. 11: 5631. https://doi.org/10.3390/ijms25115631