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Macrophage Polarization Comes of Age
Open accessAbstract
Functional polarization of macrophages into M1 or M2 cells is an operationally useful, simplified conceptual framework describing the plasticity of mononuclear phagocytes. Genetic approaches have begun to shed new light on mechanisms underlying macrophage polarization and on the actual in vivo significance of polarized M2 cells ( [this issue of Immunity]).
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“In contrast, M2 macrophages are involved in polarized Th2 inflammatory reactions and characterized by expression of arginase-1 and mannose and scavenger receptors [19], [20].”
From Rac2 Controls Tumor Growth, Metastasis and M1-M2 Macrophage Differentiation In Vivo (2014) · cites this paper as [19]
In the citing paper
“M1 macrophages are IL-12high, IL-23high, IL-10low; produce high levels of inducible nitric oxide synthetase (iNOS); secrete inflammatory cytokines such as IL-1β, IL-6, and TNF; and are inducer and effector cells in Th1 type inflammatory responses [19].”
From Rac2 Controls Tumor Growth, Metastasis and M1-M2 Macrophage Differentiation In Vivo (2014) · cites this paper as [19]
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“M2 macrophages differentiation is induced by IL-4, IL-10, IL-13, IL-21, activin A, immune complexes, and glucocorticoid and express high levels of IL-10, IL-1 receptor antagonist, CC ligand 22 (CCL22), scavenger, mannose and galactose receptors, arginase I and CD163 antigen [7, 9–14].”
BackgroundAlternatively activated myeloid (M2) cells enhance cognitive function in immune compromised mice
Derecki, N. C., Quinnies, K. M., & Kipnis, J. (2010) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2010.11.009 · Cited by 102
“In this study we show that induction of an alternatively activated (M2) phenotype of myeloid cells (Mantovani et al., 2005), achieved by skewing them in vitro with IL-4, and their subsequent injection into T cell-deficient recipients, results in the reverse of proinflammatory skew and in improved learning and memory.”
BackgroundMethodInfluentialImmune and Inflammatory Mechanisms of Atherosclerosis
Galkina, E., & Ley, K. F. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132620 · Cited by 1,480
Chung, F., Lee, K., Wang, C., Heh, C., Chan, Y., Chen, H., Kuo, C.-H. S., Feng, P., Lin, T., Wang, C., et al. (2011) · International Journal of Cancer · doi:10.1002/ijc.27403 · Cited by 101
“In some conditions, alternatively activated macrophages polarize to the M2 phenotype, which secrete matrix-degrading enzymes, angiogenic factors and immunosuppressive cytokines/chemokines that promote tumor growth and metastasis.(29) Recent reports on early-stage NSCLC demonstrate that macrophages in the tumor islet a…”
BackgroundGawda, A., Majka, G., Nowak, B., Śróttek, M., Walczewska, M., & Marcinkiewicz, J. (2018) · Inflammation Research · doi:10.1007/s00011-018-1165-4 · Cited by 71
“To determine the impact of PM and PMΔC on macrophage state of activation, the cells were pre-incubated (primed) with various concentrations of either PM or PMΔC and then activated with LPS which induces M1-like pattern of proinflammatory mediators [18].”
MethodFeng, Q., Xu, M., Yu, Y., Hou, Y., Mi, X., Sun, Y., Ma, S., Zuo, X., Shao, L., Hou, M., et al. (2017) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.13767 · Cited by 96
Wang, R. M., Johnson, T. D., He, J., Rong, Z., Wong, M., Nigam, V., Behfar, A., Xu, Y., & Christman, K. L. (2017) · Biomaterials · doi:10.1016/j.biomaterials.2017.03.016 · Cited by 90
“Macrophage polarization is plastic and complex [35e37], but is often simplified into proinflammatory M1 and pro-remodeling M2 phenotypes [38].”
BackgroundInfluentialTCR Redirected T Cells for Cancer Treatment: Achievements, Hurdles, and Goals
Manfredi, F., Cianciotti, B. C., Potenza, A., Tassi, E., Noviello, M., Biondi, A., Ciceri, F., Bonini, C., & Ruggiero, E. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01689 · Cited by 108
“M2-TAM and TEM sustain tumor survival and blunt immune reactions.”
BackgroundAlameddine, H. S., & Morgan, J. E. (2016) · Journal of Neuromuscular Diseases · doi:10.3233/jnd-160183 · Cited by 122
The interplay between central metabolism and innate immune responses
Cheng, S., Joosten, L. A. B., & Netea, M. G. (2014) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2014.06.008 · Cited by 97
“M1 macrophages are characterized by a proinflammatory phenotype producing more proinflammatory cytokines, ROS and iNOS upon stimulation, while M2 macrophages are regarded to be more anti-inflammatory, promoting tissue remodeling, tumor progression, and dampening inflammation [26].”
BackgroundMacrophages Driven to a Novel State of Activation Have Anti-Inflammatory Properties in Mice
Exner, B. G., Sattler, C., Hutchinson, J. A., Koehl, G. E., Kronenberg, K., Farkas, S. A., Inoue, S., Blank, C. A., Knechtle, S. J., Schlitt, H. J., et al. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.1.335 · Cited by 84
“Nevertheless, it is convenient to categorize macrophage subsets according to static functional and phenotypic criteria (3).”
Activation of Natural Killer T Cells Ameliorates Postinfarct Cardiac Remodeling and Failure in Mice
Sobirin, M. A., Kinugawa, S., Takahashi, M., Fukushima, A., Homma, T., Ono, T., Hirabayashi, K., Suga, T., Azalia, P., Takada, S., et al. (2012) · Circulation Research · doi:10.1161/circresaha.112.270132 · Cited by 89
“αGC increased not only M1 macrophages but also M2 macrophages, which tune inflammatory responses and promote tissue repair.(33) Therefore, the increase in M2 macrophage might neutralize the effect of the increased M1 macrophage and MCP-1.”
BackgroundBrambilla, P., Bellani, M., Isola, M., Bergami, A., Marinelli, V, Dusi, N., Rambaldelli, G., Tansella, M., Maria Finardi, A., Martino, G., et al. (2014) · Translational Psychiatry · doi:10.1038/tp.2014.46 · Cited by 86
Clinicopathologic, Immunohistochemical, and Molecular Features of Histiocytoid Sweet Syndrome
Alegría‐Landa, V., Rodríguez-Pinilla, S. M., Santos-Briz, A. J., Rodríguez‐Peralto, J. L., Alegre, V. A., Cerroni, L., Kutzner, H., & Requena, L. (2017) · JAMA Dermatology · doi:10.1001/jamadermatol.2016.6092 · Cited by 91
Stapleton, T. W., Ingram, J., Fisher, J., & Ingham, E. (2010) · Tissue Engineering. Part A · doi:10.1089/ten.tea.2009.0807 · Cited by 88
Delpech, J.-C., Madore, C., Joffre, C., Aubert, A., Kang, J. X., Nadjar, A., & Layé, S. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.196 · Cited by 105
“This phenotype is characterized by high levels of anti-inflammatory cytokines and low levels of pro-inflammatory cytokines production (Mantovani et al, 2005).”
BackgroundSHIP-deficient, alternatively activated macrophages protect mice during DSS-induced colitis
Weisser, S. B., Brugger, H. K., Voglmaier, N., McLarren, K. W., van Rooijen, N., & Sly, L. M. (2011) · Journal of Leukocyte Biology · doi:10.1189/jlb.0311124 · Cited by 94
“However, as m phenotype is plastic [17], it changes according to the local environment, so ex vivo-derived M2a m are unlikely to be an effective therapy for treatment of IBDs.”
BackgroundBurgos-Molina, A. M., Santana, T. T., Redondo, M., & Romero, M. J. B. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25116188 · Cited by 87
“M1 macrophages have proinflammatory and antimicrobial activities, while M2 macrophages participate in waste and apoptotic cell clearance and have anti-inflammatory properties [33].”
BackgroundPCB 126 induces monocyte/macrophage polarization and inflammation through AhR and NF-κB pathways
Wang, C., Petriello, M. C., Zhu, B., & Hennig, B. (2019) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2019.02.006 · Cited by 90
“spite of a spectrum of inflammatory features and functional properties, there are two main groups, classically activated and alternatively activated macrophages, also termed M1 and M2, respectively (Mantovani et al., 2005; Mosser and Edwards, 2008).”
Combatting Fibrosis: Exosome‐Based Therapies in the Regression of Liver Fibrosis
Chen, L., Brenner, D. A., & Kisseleva, T. (2018) · Hepatology Communications · doi:10.1002/hep4.1290 · Cited by 93
“Various types of macrophages, such as M1 (inflammatory), M2a-like (profibrotic), and Mregulatory/M2c-like (regulatory), (73,75-77,80,81) are recruited during fibrogenesis, resulting in reepithelization, healing, or pathologic scarring.”
BackgroundMicroRNAs in immune regulation—Opportunities for cancer immunotherapy
Okada, H., Kohanbash, G., & Lotze, M. T. (2010) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2010.02.002 · Cited by 87
“Macrophage miRs in Development Myeloid cells including monocytes and macrophages regulate tissue homeostasis and local inflammation/immunity, differentiating into various cell types in response to provocative stimuli (Mantovani et al., 2005, Randolph et al., 2002, Chomarat et al., 2003).”
BackgroundHide-and-seek: the interplay between cancer stem cells and the immune system
Sultan, M., Coyle, K. M., Vidovic, D., Thomas, M. L., Gujar, S. A., & Marcato, P. (2016) · Carcinogenesis · doi:10.1093/carcin/bgw115 · Cited by 98
Selective inhibition and augmentation of alternative macrophage activation by progesterone
Menzies, F. M., Henriquez, F. L., Alexander, J. K., & Roberts, C. W. (2011) · Immunology · doi:10.1111/j.1365-2567.2011.03488.x · Cited by 100
Effects of Curcumin on Microglial Cells
Ghasemi, F., Bagheri, H., Barreto, G. E., Read, M. I., & Sahebkar, A. (2019) · Neurotoxicity Research · doi:10.1007/s12640-019-00030-0 · Cited by 97
Macrophage Silica Nanoparticle Response is Phenotypically Dependent
Herd, H. L., Bartlett, K., Gustafson, J. A., Mcgill, L., & Ghandehari, H. (2015) · Biomaterials · doi:10.1016/j.biomaterials.2015.02.070 · Cited by 84
Trophoblast Induces Monocyte Differentiation Into CD 14+/ CD 16+ Macrophages
Aldo, P. B., Racicot, K. E., Craviero, V., Guller, S. M., Romero, R. J., & Mor, G. (2014) · American Journal of Reproductive Immunology · doi:10.1111/aji.12288 · Cited by 87
Endogenous Epoxygenases Are Modulators of Monocyte/Macrophage Activity
Bystrom, J., Wray, J., Sugden, M., Holness, M., Swales, K., Warner, T., Edin, M., Zeldin, D., Gilroy, D., & Bishop-Bailey, D. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026591 · Cited by 84
“wound healing, repair and chronic inflammation [1].”
BackgroundDendritic Cells: A Critical Player in Cancer Therapy?
Palucka, A. K., Ueno, H., Fay, J. W., & Banchereau, J. (2008) · Journal of Immunotherapy · doi:10.1097/cji.0b013e31818403bc · Cited by 80
“Finally, drugs, such as cyclooxygenase-2 inhibitors,(146) might permit to improve outcomes by blocking inflammation that allows tumor progression.(171,172) In this context, it is important to consider tumor microenvironment.”
BackgroundWenzek, C., Boelen, A., Westendorf, A. M., Engel, D. R., Moeller, L. C., & Führer-Sakel, D. (2022) · European Journal of Endocrinology · doi:10.1530/eje-21-1171 · Cited by 125
Chen, Q., Zhang, K., Jin, Y., Zhu, T., Cheng, B., Shu, Q., & Fang, X. (2013) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201211-1967oc · Cited by 87
Metadata
- Authors
- Mantovani, Sica, & Locati, M.
- Affiliations
- University of Milan (IT)
- Corresponding author
- Mantovani,, Alberto
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2005-10
- Volume
- 23
- Issue
- 4
- Pages
- 344-346
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W1986736465
- Cited by
- 1,259
- References
- 0
- Citations by year
- 2026: 41 · 2025: 60 · 2024: 58 · 2023: 54 · 2022: 70 · 2021: 65 · 2020: 68 · 2019: 58 · 2018: 57 · 2017: 70 · 2016: 67 · 2015: 64 · 2014: 85 · 2013: 89 · 2012: 80
- FWCI
- 9.96
- 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, 2846 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)
- Funders
- Ministero dell’Istruzione, dell’Università e della Ricerca
- Associazione Italiana per la Ricerca sul Cancro
- European Commission
- Ministero della Salute
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- macrophage polarization, M1 macrophages, M2 macrophages, mononuclear phagocytes, macrophage plasticity
- MeSH terms
- Cell Differentiation, Macrophages
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