The DOI matches its Crossref record; 46 of the 47 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
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.
In the citing paper
“which secrete anti-inflammatory cytokines/growth factors9.”
From M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination (2013) · cites this paper as [9]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
1 retracted
Melendez, A. J., & Ibrahim, F. B. M. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.3.1596 · Cited by 90
RetractedPathogen Recognition and Innate Immunity
Akira, S., Uematsu, S., & Takeuchi, O. (2006) · Cell · doi:10.1016/j.cell.2006.02.015 · Cited by 11,976
The chemokine system in diverse forms of macrophage activation and polarization
MANTOVANI, A., SICA, A., SOZZANI, S., ALLAVENA, P., VECCHI, A., & LOCATI, M. (2004) · Trends in Immunology · doi:10.1016/j.it.2004.09.015 · Cited by 6,534
MANTOVANI, A., SOZZANI, S., LOCATI, M., ALLAVENA, P., & SICA, A. (2002) · Trends in Immunology · doi:10.1016/s1471-4906(02)02302-5 · Cited by 5,528
Stein, M., Keshav, S., Harris, N., & Gordon, S. (1992) · The Journal of experimental medicine · doi:10.1084/jem.176.1.287 · Cited by 1,960
Stuehr, D. J., & Nathan, C. F. (1989) · The Journal of Experimental Medicine · doi:10.1084/jem.169.5.1543 · Cited by 1,744
Induction by Antigen of Intrathymic Apoptosis of CD4 + CD8 + TCR lo Thymocytes in Vivo
MURPHY, K. M. M., Heimberger, A. B., & Loh, D. Y. (1990) · Science · doi:10.1126/science.2125367 · Cited by 1,714
Nathan, C., & Shiloh, M. U. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.16.8841 · Cited by 1,469
Stout, R. D., Jiang, C., Matta, B., Tietzel, I., Watkins, S. K., & Suttles, J. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.1.342 · Cited by 968
Alarmins: chemotactic activators of immune responses
Oppenheim, J. J., & Yang, D. (2005) · Current Opinion in Immunology · doi:10.1016/j.coi.2005.06.002 · Cited by 780
Hesse, M., Modolell, M., Flamme, A. C. L., Schito, M. L., Fuentes, J. M., Cheever, A. W., Pearce, E. J., & Wynn, T. A. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.11.6533 · Cited by 723
Biswas, S. K. (2005) · Blood · doi:10.1182/blood-2005-01-0428 · Cited by 691
Holcomb, I. N., Kabakoff, R. C., Chan, B., Baker, T. W., Gurney, A. L., Henzel, W. J., Nelson, C., Lowman, H. B., Wright, B. D., Skelton, N. J., et al. (2000) · The EMBO Journal · doi:10.1093/emboj/19.15.4046 · Cited by 662
Shaping Gene Expression in Activated and Resting Primary Macrophages by IL-10
Lang, R., Patel, D. H., Morris, J. J., Rutschman, R., & Murray, P. J. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.5.2253 · Cited by 621
Modolell, M., Corraliza, I. M., Link, F., Soler, G., & Eichmann, K. (1995) · European Journal of Immunology · doi:10.1002/eji.1830250436 · Cited by 554
Determination of arginase activity in macrophages: a micromethod
Corraliza, I., Campo, M. L., Soler, G., & Modolell, M. (1994) · Journal of Immunological Methods · doi:10.1016/0022-1759(94)90027-2 · Cited by 544
Tamada, K., Shimozaki, K., Chapoval, A. I., Zhai, Y., Su, J., Chen, S.-F., Hsieh, S.-L. E., Nagata, S., Ni, J., & Chen, L. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.8.4105 · Cited by 395
Temporal expression of different pathways of 1-arginine metabolism in healing wounds.
Albina, J. E., Mills, C. D., Henry, W. L., & Caldwell, M. D. (1990) · The Journal of Immunology · doi:10.4049/jimmunol.144.10.3877 · Cited by 351
A novel phenotype for an activated macrophage: the type 2 activated macrophage
Anderson, C. F., & Mosser, D. M. (2002) · Journal of Leukocyte Biology · doi:10.1189/jlb.72.1.101 · Cited by 347
Self-citationKwon, B. S., Tan, K. B., Ni, J., Lee, Z. H., Kim, K. K., Kim, Y.-J., Wang, S., Gentz, R., Yu, G., Harrop, J., et al. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.22.14272 · Cited by 303
Gratchev, A., Guillot, P., Hakiy, N., Politz, O., Orfanos, C. E., Schledzewski, K., & Goerdt, S. (2001) · Scandinavian Journal of Immunology · doi:10.1046/j.1365-3083.2001.00885.x · Cited by 300
Reversing Lipopolysaccharide Toxicity by Ligating the Macrophage Fcγ Receptors
Gerber, J. S., & Mosser, D. M. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.11.6861 · Cited by 263
Self-citationA role for IgG immune complexes during infection with the intracellular pathogen Leishmania
Miles, S. A., Conrad, S. M., Alves, R. G., Jerônimo, S. M. B., & Mosser, D. M. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20041470 · Cited by 262
Self-citationNair, M. G., Gallagher, I. J., Taylor, M. D., Loke, P., Coulson, P. S., Wilson, R. A., Maizels, R. M., & Allen, J. E. (2004) · Infection and Immunity · doi:10.1128/iai.73.1.385-394.2005 · Cited by 252
Kodelja, V., Müller, C., Politz, O., Hakij, N., Orfanos, C. E., & Goerdt, S. (1998) · PubMed · Cited by 249
Willment, J. A., Lin, H.-H., Reid, D. M., Taylor, P. R., Williams, D. L., Wong, S. Y. C., Gordon, S., & Brown, G. D. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.9.4569 · Cited by 238
Skeen, M. J., Miller, M. A., Shinnick, T. M., & Ziegler, H. (1996) · The Journal of Immunology · doi:10.4049/jimmunol.156.3.1196 · Cited by 231
Kodelja, V., Müller, C., Politz, O., Hakij, N., Orfanos, C. E., & Goerdt, S. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.160.3.1411 · Cited by 223
Similarities between interleukin-2 receptor number and affinity on activated B and T lymphocytes
Lowenthal, J. W., Zubler, R. H., Nabholz, M., & MacDonald, H. R. (1985) · Nature · doi:10.1038/315669a0 · Cited by 189
Cutting Edge: Biasing Immune Responses by Directing Antigen to Macrophage Fcγ Receptors1
Anderson, C. F., & Mosser, D. (2002) · Journal of Immunology · doi:10.4049/jimmunol.168.8.3697 · Cited by 187
Self-citationMechanisms of L-selectin regulation by activated T cells
Chao, C., Jensen, R. J., & Dailey, M. O. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.159.4.1686 · Cited by 168
Yokoyama, W. M., Koning, F., Kehn, P. J., Pereira, G. M. B., Stingl, G., Coligan, J. E., & Shevach, E. M. (1988) · The Journal of Immunology · doi:10.4049/jimmunol.141.2.369 · Cited by 157
FIZZ1 and Ym as Tools to Discriminate between Differentially Activated Macrophages
Raes, G., Noël, W., Beschin, A., Brys, L., BAETSELIER, P. D., & Hassanzadeh, G. G. (2002) · Journal of Immunology Research · doi:10.1080/1044667031000137629 · Cited by 147
Transcriptional Profiling Reveals Complex Regulation of the Monocyte IL-1β System by IL-13
Scotton, C. J., Martínez, F. O., Smelt, M. J., Sironi, M., Locati, M., Mantovani, A., & Sozzani, S. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.2.834 · Cited by 142
Brys, L., Beschin, A., Raes, G., Ghassabeh, G. H., Noël, W., Brandt, J., Brombacher, F., & BAETSELIER, P. D. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.10.6095 · Cited by 138
Schebesch, C., Kodelja, V., Müller, C., Hakij, N., Bisson, S., Orfanos, C. E., & Goerdt, S. (1997) · Immunology · doi:10.1046/j.1365-2567.1997.00371.x · Cited by 121
Kihara, A., Anada, Y., & Igarashi, Y. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m510308200 · Cited by 91
Mouse T cells receive costimulatory signals from LIGHT, a TNF family member
Shi, G., Luo, H., Wan, X., Salcedo, T. W., Zhang, J., & Wu, J. (2002) · Blood · doi:10.1182/blood-2002-05-1404 · Cited by 83
Kambayashi, T., Jacob, C. O., & Strassmann, G. (1996) · Cellular Immunology · doi:10.1006/cimm.1996.0186 · Cited by 78
Sphingosine Kinase Protects Lipopolysaccharide-Activated Macrophages from Apoptosis
Wu, W., Mosteller, R. D., & Broek, D. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.17.7359-7369.2004 · Cited by 74
A TNF Family Member LIGHT Transduces Costimulatory Signals into Human T Cells
Wan, X., Zhang, J., Luo, H., Shi, G., Kapnik, E. M., Kim, S., Kanakaraj, P., & Wu, J. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.12.6813 · Cited by 74
A method for the derivation and continuous propagation of cloned murine bone marrow macrophages
Johnson, C. R., Kitz, D. J., & Little, J. R. (1983) · Journal of Immunological Methods · doi:10.1016/0022-1759(83)90127-8 · Cited by 63
Macrophage activation by lymphocyte mediators.
David, D. (1975) · PubMed · Cited by 60
Mortarini, R., Scarito, A., Nonaka, D., Zanon, M., Bersani, I., Montaldi, E., Pennacchioli, E., Patuzzo, R., Santinami, M., & Anichini, A. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-3239 · Cited by 39
Frankenberger, M., Häussinger, K., & Ziegler-Heitbrock, L. (2004) · International Immunopharmacology · doi:10.1016/j.intimp.2004.09.033 · Cited by 30
Sphingosine Kinase 1 Is a Negative Regulator of CD4+ Th1 Cells
Yang, J., Castle, B. E., Hanidu, A., Stevens, L. M., Yu, Y., Li, X., Stearns, C. D., Papov, V. V., Rajotte, D., & Li, J. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.10.6580 · Cited by 28
Flagged first, then by citations
1 of the 47 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- 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
Cited by
Sorted by citations
Exploring the full spectrum of macrophage activation
Mosser, D. M., & Edwards, J. P. (2008) · Nature Reviews Immunology · doi:10.1038/nri2448 · Cited by 9,144
Self-citationMacrophage activation and polarization: nomenclature and experimental guidelines
Murray, P. J., Allen, J. E., Biswas, S. K., Fisher, E. A., Gilroy, D. W., Goerdt, S., Gordon, S., Hamilton, J. A., Ivashkiv, L. B., Lawrence, T., et al. (2014) · Immunity · doi:10.1016/j.immuni.2014.06.008 · Cited by 6,337
Self-citationThe M1 and M2 paradigm of macrophage activation: Time for reassessment
Martinez, F. O., & Gordon, S. (2014) · F1000Prime Reports · doi:10.12703/p6-13 · Cited by 4,689
Macrophage activation and polarization
Martinez, F. O. (2008) · Frontiers in Bioscience · doi:10.2741/2692 · Cited by 3,160
Murray, P. J. (2017) · Annual Review of Physiology · doi:10.1146/annurev-physiol-022516-034339 · Cited by 2,981
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
