Cited by 312Immune cells in cancerRedox biology and oxidative stressNeutrophil, Myeloperoxidase and Oxidative Mechanisms

Macrophage Polarization and Reprogramming in Acute Inflammation: A Redox Perspective

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Pérez, Salvador, Rius-Pérez, Sergio·2022·Antioxidants

Abstract

Macrophage polarization refers to the process by which macrophages can produce two distinct functional phenotypes: M1 or M2. The balance between both strongly affects the progression of inflammatory disorders. Here, we review how redox signals regulate macrophage polarization and reprogramming during acute inflammation. In M1, macrophages augment NADPH oxidase isoform 2 (NOX2), inducible nitric oxide synthase (iNOS), synaptotagmin-binding cytoplasmic RNA interacting protein (SYNCRIP), and tumor necrosis factor receptor-associated factor 6 increase oxygen and nitrogen reactive species, which triggers inflammatory response, phagocytosis, and cytotoxicity. In M2, macrophages down-regulate NOX2, iNOS, SYNCRIP, and/or up-regulate arginase and superoxide dismutase type 1, counteract oxidative and nitrosative stress, and favor anti-inflammatory and tissue repair responses. M1 and M2 macrophages exhibit different metabolic profiles, which are tightly regulated by redox mechanisms. Oxidative and nitrosative stress sustain the M1 phenotype by activating glycolysis and lipid biosynthesis, but by inhibiting tricarboxylic acid cycle and oxidative phosphorylation. This metabolic profile is reversed in M2 macrophages because of changes in the redox state. Therefore, new therapies based on redox mechanisms have emerged to treat acute inflammation with positive results, which highlights the relevance of redox signaling as a master regulator of macrophage reprogramming.

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Crossref · 10.3390/antiox11071394

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  • M1 macrophages produce intracellular nitric oxide by iNOS and superoxide anion O2•− and subsequent reactive species, which are cytotoxic to microbial agents and fight infection.

    “M1 macrophages produce intracellular nitric oxide •NO by inducible nitric oxide synthase iNOS and superoxide anion O2•− and subsequent reactive species, which are cytotoxic to microbial agents and fight infection [195].”

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Authors
Pérez, S., & Rius-Pérez, S.
Affiliations
  • Universitat de València (ES)
  • Department of Physiology, Faculty of Pharmacy, University of Valencia, Burjasot, 46100 Valencia, Spain
Corresponding author
Pérez, Salvador
Venue
Antioxidants
Publisher
MDPI AG
Published
2022-07-19
Volume
11
Issue
7
Pages
1394
ISSN
2076-3921 (ISSN-L)
OpenAlex
W4285794323
Cited by
312
References
191
Citations by year
2026: 75 · 2025: 118 · 2024: 76 · 2023: 36 · 2022: 7
FWCI
6.25
Type
journal article
Language
en
Open access
Locations
  • Antioxidants (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Generalitat Valenciana, Conselleria d’Educació, Investigació, Cultura I Esport (GV/2021/150)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Keywords
macrophage polarization, M1/M2 macrophages, acute inflammation, redox signaling, oxidative stress, nitrosative stress, NADPH oxidase 2, inducible nitric oxide synthase, SYNCRIP, TRAF6, arginase, superoxide dismutase 1, macrophage metabolism, glycolysis, lipogenesis, TCA cycle, oxidative phosphorylation, anti-inflammatory therapy

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