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Cited by 863Immune cells in cancerPhagocytosis and Immune RegulationImmune Response and Inflammation

Biochemical and functional characterization of three activated macrophage populations

Open access
Edwards, Justin P, Zhang, Xia, Frauwirth, Kenneth A, Mosser, David M·2006·Journal of Leukocyte Biology
DOI 10.1189/jlb.0406249PMC PMC2642590
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Abstract

We generated three populations of macrophages (Mφ) in vitro and characterized each. Classically activated Mφ (Ca-Mφ) were primed with IFN-γ and stimulated with LPS. Type II-activated Mφ (Mφ-II) were similarly primed but stimulated with LPS plus immune complexes. Alternatively activated Mφ (AA-Mφ) were primed overnight with IL-4. Here, we present a side-by-side comparison of the three cell types. We focus primarily on differences between Mφ-II and AA-Mφ, as both have been classified as M2 Mφ, distinct from Ca-Mφ. We show that Mφ-II more closely resemble Ca-Mφ than they are to AA-Mφ. Mφ-II and Ca-Mφ, but not AA-Mφ, produce high levels of NO and have low arginase activity. AA-Mφ express FIZZ1, whereas neither Mφ-II nor Ca-Mφ do. Mφ-II and Ca-Mφ express relatively high levels of CD86, whereas AA-Mφ are virtually devoid of this costimulatory molecule. Ca-Mφ and Mφ-II are efficient APC, whereas AA-Mφ fail to stimulate efficient T cell proliferation. The differences between Ca-Mφ and Mφ-II are more subtle. Ca-Mφ produce IL-12 and give rise to Th1 cells, whereas Mφ-II produce high levels of IL-10 and thus, give rise to Th2 cells secreting IL-4 and IL-10. Mφ-II express two markers that may be used to identify them in tissue. These are sphingosine kinase-1 and LIGHT (TNF superfamily 14). Thus, Ca-Mφ, Mφ-II, and AA-Mφ represent three populations of cells with different biological functions.

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Crossref · 10.1189/jlb.0406249

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  • Regenerative properties of microglia/macrophages following injury to muscle and skin are associated with alternative or deactivation to M2-polarized phenotypes (M2a and M2c, respectively).

    “Regenerative properties of microglia/macrophages following injury to muscle6, 7 and skin8 are associated with alternative or deactivation to M2-polarized phenotypes (M2a and M2c, respectively), which secrete anti-inflammatory cytokines/growth factors9.”

    From M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination (2013) · cites this paper as [9]

    The Introduction (page unavailable) says type II-activated macrophages secrete IL-10, making them anti-inflammatory. That supports the anti-inflammatory cytokine portion of the statement cited to this paper, but the cited passages do not establish secretion of growth factors or that both named M2 phenotypes secrete them. The muscle- and skin-injury portions carry different citations. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • M2-polarized phenotypes secrete anti-inflammatory cytokines/growth factors.

    “which secrete anti-inflammatory cytokines/growth factors9.”

    From M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination (2013) · cites this paper as [9]

    The Introduction identifies both type II-activated and alternatively activated macrophages as M2 phenotypes, and the Results report that type II-activated macrophages secrete high levels of the anti-inflammatory cytokine IL-10. But the Results also report that alternatively activated macrophages secreted no detectable IL-10 under the tested conditions; the cited passages do not establish growth-factor secretion. The claim therefore overgeneralizes across M2 phenotypes. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • M1 'classically activated' phenotypes are associated with enhanced antigen presentation properties and secretion of pro-inflammatory cytokines and reactive oxygen/nitrogen species.

    “In contrast, M1 ‘classically activated’ phenotypes are associated with enhanced antigen presentation properties and secretion of pro-inflammatory cytokines and reactive oxygen/nitrogen species9.”

    From M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination (2013) · cites this paper as [9]

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Authors
Edwards, J. P., Zhang, X., Frauwirth, K. A., & Mosser, D. M.
Affiliations
University of Maryland, College Park (US)
Corresponding author
Mosser, David M
ORCID
Venue
Journal of Leukocyte Biology
Publisher
Oxford University Press (OUP)
Published
2006-08-11
Volume
80
Issue
6
Pages
1298-1307
ISSN
  • 0741-5400 (ISSN-L)
  • 1938-3673
DOI
10.1189/jlb.0406249
PMC
PMC2642590
OpenAlex
W2168203604
Cited by
863
References
47
Citations by year
2026: 14 · 2025: 21 · 2024: 34 · 2023: 25 · 2022: 45 · 2021: 51 · 2020: 49 · 2019: 44 · 2018: 45 · 2017: 43 · 2016: 48 · 2015: 78 · 2014: 62 · 2013: 61 · 2012: 47
FWCI
10.22
Type
journal article
Language
en
Open access
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations
  • Journal of Leukocyte Biology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health (AI49383)
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 › Immune Response and Inflammation
Keywords
macrophage polarization, M1 macrophages, M2 macrophages, interferon-gamma, LPS, immune complexes, IL-4, nitric oxide, arginase, Fizz1, CD86, antigen presentation, T cell proliferation, IL-12, IL-10, Th1/Th2 differentiation, sphingosine kinase 1, light
MeSH terms
Sphingosine Kinase, Animals, Arginase, Cells, Cultured, Lipopolysaccharides, Macrophage Activation, Macrophages, Mice, Inbred BALB C, Nitric Oxide, Proteins, Cytokines, Phosphotransferases (Alcohol Group Acceptor), Th1 Cells, Th2 Cells, Coculture Techniques, Nerve Growth Factor, Intercellular Signaling Peptides and Proteins, Cell Proliferation, Mice, B7-2 Antigen, Tumor Necrosis Factor Ligand Superfamily Member 14

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