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

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Biochemical and functional characterization of three activated macrophage populations

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Edwards, Justin P, Zhang, Xia, Frauwirth, Kenneth A, Mosser, David M·2006·Journal of Leukocyte Biology

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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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Antisense Knockdown of Sphingosine Kinase 1 in Human Macrophages Inhibits C5a Receptor-Dependent Signal Transduction, Ca2+ Signals, Enzyme Release, Cytokine Production, and Chemotaxis
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Anderson, 2002, A novel phenotype for an activated macrophage: the type 2 activated macrophage, J. Leukoc. Biol., 72, 101, 10.1189/jlb.72.1.101 · DOI

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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: Edwards, Justin P
Zhang, Xia
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
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: green
www.ncbi.nlm.nih.gov
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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Biochemical and functional characterization of three activated macrophage populations

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