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Biochemical and functional characterization of three activated macrophage populations
Open accessAbstract
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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“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]
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“which secrete anti-inflammatory cytokines/growth factors9.”
From M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination (2013) · cites this paper as [9]
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“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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Metadata
- Authors
- Edwards, J. P., Zhang, X., Frauwirth, K. A., & Mosser, D. M.
- Affiliations
- University of Maryland, College Park (US)
- Corresponding author
- Mosser, David M
- 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
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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