Macrophage Polarization in Hypoxia and Ischemia/reperfusion: Insights into the Role of Energetic Metabolism

Overview

Journal Exp Biol Med (Maywood)

Specialty Biology

Date 2022 Feb 28

PMID 35220781

Authors

Elmira I Yakupova

Grigoriy V Maleev

Andrei V Krivtsov

Egor Y Plotnikov

Affiliations

Soon will be listed here.

Abstract

Macrophages, the key cells of innate immunity, possess wide phenotypical and functional heterogeneity. studies showed that microenvironment signals could induce the so-called polarization of macrophages into two phenotypes: classically activated macrophages (M1) or alternatively activated macrophages (M2). Functionally, they are considered as proinflammatory and anti-inflammatory/pro-regenerative, respectively. However, studies into macrophage states revealed a continuum of phenotypes from M1 to M2 state instead of the clearly distinguished extreme phenotypes. An important role in determining the type of polarization of macrophages is played by energy metabolism, including the activity of oxidative phosphorylation. In this regard, hypoxia and ischemia that affect cellular energetics can modulate macrophage polarization. Here, we overview the data on macrophage polarization during metabolic shift-associated pathologies including ischemia and ischemia/reperfusion in various organs and discuss the role of energy metabolism potentially triggering the macrophage polarization.

Citing Articles

The effect of macrophages and their exosomes in ischemic heart disease.

Wang M, Li C, Liu Y, Jin Y, Yu Y, Tan X Front Immunol. 2024; 15:1402468.

PMID: 38799471 PMC: 11116575. DOI: 10.3389/fimmu.2024.1402468.

Anti-Inflammatory Effect of Synaptamide in Ischemic Acute Kidney Injury and the Role of G-Protein-Coupled Receptor 110.

Brezgunova A, Andrianova N, Saidova A, Potashnikova D, Abramicheva P, Manskikh V Int J Mol Sci. 2024; 25(3).

PMID: 38338779 PMC: 10855239. DOI: 10.3390/ijms25031500.

5-aminolevulinate and CHIL3/CHI3L1 treatment amid ischemia aids liver metabolism and reduces ischemia-reperfusion injury.

Jin G, Guo N, Liu Y, Zhang L, Chen L, Dong T Theranostics. 2023; 13(14):4802-4820.

PMID: 37771779 PMC: 10526663. DOI: 10.7150/thno.83163.

Macrophage-Driven Inflammation in Metabolic Osteoarthritis: Implications for Biomarker and Therapy Development.

Warmink K, Vinod P, Korthagen N, Weinans H, Rios J Int J Mol Sci. 2023; 24(7).

PMID: 37047082 PMC: 10094694. DOI: 10.3390/ijms24076112.

Inflammation and vascular remodeling in COVID-19 hearts.

Werlein C, Ackermann M, Stark H, Shah H, Tzankov A, Haslbauer J Angiogenesis. 2022; 26(2):233-248.

PMID: 36371548 PMC: 9660162. DOI: 10.1007/s10456-022-09860-7.

References

Vats D, Mukundan L, Odegaard J, Zhang L, Smith K, Morel C . Oxidative metabolism and PGC-1beta attenuate macrophage-mediated inflammation. Cell Metab. 2006; 4(1):13-24. PMC: 1904486. DOI: 10.1016/j.cmet.2006.05.011. View

Zhang N, Liu C, Jin L, Zhang R, Wang T, Wang Q . Ketogenic Diet Elicits Antitumor Properties through Inducing Oxidative Stress, Inhibiting MMP-9 Expression, and Rebalancing M1/M2 Tumor-Associated Macrophage Phenotype in a Mouse Model of Colon Cancer. J Agric Food Chem. 2020; 68(40):11182-11196. DOI: 10.1021/acs.jafc.0c04041. View

Nahrendorf M, Swirski F . Abandoning M1/M2 for a Network Model of Macrophage Function. Circ Res. 2016; 119(3):414-7. PMC: 4965179. DOI: 10.1161/CIRCRESAHA.116.309194. View

Sachithanandan N, Graham K, Galic S, Honeyman J, Fynch S, Hewitt K . Macrophage deletion of SOCS1 increases sensitivity to LPS and palmitic acid and results in systemic inflammation and hepatic insulin resistance. Diabetes. 2011; 60(8):2023-31. PMC: 3142066. DOI: 10.2337/db11-0259. View

Lewis J, Lee J, Underwood J, Harris A, Lewis C . Macrophage responses to hypoxia: relevance to disease mechanisms. J Leukoc Biol. 1999; 66(6):889-900. DOI: 10.1002/jlb.66.6.889. View

Hesse M, Modolell M, La Flamme A, Schito M, Fuentes J, CHEEVER A . Differential regulation of nitric oxide synthase-2 and arginase-1 by type 1/type 2 cytokines in vivo: granulomatous pathology is shaped by the pattern of L-arginine metabolism. J Immunol. 2001; 167(11):6533-44. DOI: 10.4049/jimmunol.167.11.6533. View

Dong Z, Wei H, Sun R, Tian Z . The roles of innate immune cells in liver injury and regeneration. Cell Mol Immunol. 2007; 4(4):241-52. View

Mouton A, DeLeon-Pennell K, Rivera Gonzalez O, Flynn E, Freeman T, Saucerman J . Mapping macrophage polarization over the myocardial infarction time continuum. Basic Res Cardiol. 2018; 113(4):26. PMC: 5986831. DOI: 10.1007/s00395-018-0686-x. View

Yoshidome H, Kato A, Edwards M, Lentsch A . Interleukin-10 suppresses hepatic ischemia/reperfusion injury in mice: implications of a central role for nuclear factor kappaB. Hepatology. 1999; 30(1):203-8. DOI: 10.1002/hep.510300120. View

10.

Vishnyakova P, Poltavets A, Nikitina M, Muminova K, Potapova A, Vtorushina V . Preeclampsia: inflammatory signature of decidual cells in early manifestation of disease. Placenta. 2021; 104:277-283. DOI: 10.1016/j.placenta.2021.01.011. View

11.

Zhang M, Yao B, Yang S, Jiang L, Wang S, Fan X . CSF-1 signaling mediates recovery from acute kidney injury. J Clin Invest. 2012; 122(12):4519-32. PMC: 3533529. DOI: 10.1172/JCI60363. View

12.

Poltavets A, Vishnyakova P, Elchaninov A, Sukhikh G, Fatkhudinov T . Macrophage Modification Strategies for Efficient Cell Therapy. Cells. 2020; 9(6). PMC: 7348902. DOI: 10.3390/cells9061535. View

13.

Prins M . Diet, ketones, and neurotrauma. Epilepsia. 2008; 49 Suppl 8:111-3. PMC: 2652873. DOI: 10.1111/j.1528-1167.2008.01852.x. View

14.

Luo W, Ai L, Wang B, Wang L, Gan Y, Liu C . Eccentric exercise and dietary restriction inhibits M1 macrophage polarization activated by high-fat diet-induced obesity. Life Sci. 2020; 243:117246. DOI: 10.1016/j.lfs.2019.117246. View

15.

Owen O, Morgan A, Kemp H, Sullivan J, Herrera M, Cahill Jr G . Brain metabolism during fasting. J Clin Invest. 1967; 46(10):1589-95. PMC: 292907. DOI: 10.1172/JCI105650. View

16.

Barakat R, Redzic Z . The Role of Activated Microglia and Resident Macrophages in the Neurovascular Unit during Cerebral Ischemia: Is the Jury Still Out?. Med Princ Pract. 2015; 25 Suppl 1:3-14. PMC: 5588523. DOI: 10.1159/000435858. View

17.

Chouchani E, Pell V, Gaude E, Aksentijevic D, Sundier S, Robb E . Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Nature. 2014; 515(7527):431-435. PMC: 4255242. DOI: 10.1038/nature13909. View

18.

Murdoch C, Muthana M, Lewis C . Hypoxia regulates macrophage functions in inflammation. J Immunol. 2005; 175(10):6257-63. DOI: 10.4049/jimmunol.175.10.6257. View

19.

Egners A, Erdem M, Cramer T . The Response of Macrophages and Neutrophils to Hypoxia in the Context of Cancer and Other Inflammatory Diseases. Mediators Inflamm. 2016; 2016:2053646. PMC: 4789443. DOI: 10.1155/2016/2053646. View

20.

Palma A, Jarrah A, Tieri P, Cesareni G, Castiglione F . Gene Regulatory Network Modeling of Macrophage Differentiation Corroborates the Continuum Hypothesis of Polarization States. Front Physiol. 2018; 9:1659. PMC: 6278720. DOI: 10.3389/fphys.2018.01659. View