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Alternative Activation of Macrophages: Mechanism and Functions
Open accessAbstract
The concept of an alternative pathway of macrophage activation has stimulated interest in its definition, mechanism, and functional significance in homeostasis and disease. We assess recent research in this field, argue for a restricted definition, and explore pathways by which the T helper 2 (Th2) cell cytokines interleukin-4 (IL-4) and IL-13 mediate their effects on macrophage cell biology, their biosynthesis, and responses to a normal and pathological microenvironment. The stage is now set to gain deeper insights into the role of alternatively activated macrophages in immunobiology.
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“A pro-inflammatory macrophage phenotype correlates with elevated expression of Tumor Necrosis Factor α (TNF α), Interleukin 1 (IL1), and Interferon Regulatory Factor 5 (IRF5)44, 45, 46.”
From Size- and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates (2015) · cites this paper as [46]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“The sebum lipids linoleic and oleic acid were detected to be potent inducers of the so-called alternative macrophage activation, which is the characteristic activation pathway for macrophages involved in tissue homeostasis and repair functions.64”
From Sebaceous-immunobiology is orchestrated by sebum lipids (2017) · cites this paper as [64]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“These cells are inherently heterogeneous and display remarkable functional plasticity, categorizing into two major phenotypes: M1 and M2 [3, 4].”
From miR-223 accelerates lipid droplets clearance in microglia following spinal cord injury by upregulating ABCA1 (2024) · cites this paper as [3]
Experimental — accuracy not yet measuredIn the citing paper
“A pro-wound healing phenotype of macrophage correlates with up regulation in expression of Dendritic Cell Immune Receptor (Dcir), Stabilin 1 (Stab1), chemokine (C-C motif) ligand 22 (CCL22), Chitinase-like 3 (YM1), and Arginase 1 (Arg1)44, 45, 46.”
From Size- and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates (2015) · cites this paper as [46]
In the citing paper
“Meanwhile, a regulatory macrophage phenotype has been characterized to correlate with elevated expression of Interleukin 10 (IL10), TNF superfamily member 14 (Light), and Sphingosine Kinase 1 (Sphk1)44, 45, 46.”
From Size- and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates (2015) · cites this paper as [46]
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“In general, M1s or classically activated MΦs are pro-inflammatory and microbicidal, whereas M2s or alternatively activated MΦs are immunomodulatory, reparative, and poorly microbicidal [7–12].”
From Macrophage functional polarization (M1/M2) in response to varying fiber and pore dimensions of electrospun scaffolds (2013) · cites this paper as [9]
In the citing paper
“Stimulation of macrophages using IL-4 or IL-10 results in alternative activation, or M2 type polarization, characterized by the release of anti-inflammatory and tissue repair molecules (41).”
From The impact of ageing on monocytes and macrophages (2021) · cites this paper as [41]
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“previous studies have shown that phosphorylation of STAT6 is a key step downstream in the IL-4 cascade that leads to Arg1 expression (49–51).”
From Trem2 promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions (2020) · cites this paper as [51]
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Metadata
- Authors
- Gordon, S., & Martinez, F. O.
- Affiliations
- University of Oxford (GB)
- Corresponding author
- Gordon, Siamon
- ORCID
- Gordon, Siamon
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2010-05
- Volume
- 32
- Issue
- 5
- Pages
- 593-604
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2065210647
- Cited by
- 4,197
- References
- 118
- Citations by year
- 2026: 193 · 2025: 255 · 2024: 262 · 2023: 292 · 2022: 319 · 2021: 318 · 2020: 292 · 2019: 251 · 2018: 249 · 2017: 271 · 2016: 244 · 2015: 289 · 2014: 283 · 2013: 277 · 2012: 226
- FWCI
- 17.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1209 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Open Research (University of Surrey) (submittedVersion)
- Funders
- British Heart Foundation
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- alternative macrophage activation, M2 macrophages, Th2 cytokines, IL-4, IL-13, macrophage polarization, macrophage homeostasis
- MeSH terms
- Animals, Humans, Macrophage Activation, Macrophages, Models, Biological, Neoplasms, Signal Transduction, Cytokines, Receptors, Interleukin
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