Global InformationMacrophage polarization information
Macrophage polarization is a process by which macrophages adopt different functional programs in response to the signals from their microenvironment. This ability is connected to their multiple roles in the organism: they are powerful effector cells of the innate immune system, but also important in removal of cellular debris, embryonic development and tissue repair.[1]
By simplified classification, macrophage phenotype has been divided into 2 groups: M1 (classically activated macrophages) and M2 (alternatively activated macrophages). This broad classification was based on in vitro studies, in which cultured macrophages were treated with molecules that stimulated their phenotype switching to a particular state.[2] In addition to chemical stimulation, it has been shown that the stiffness of the underlying substrate a macrophage is grown on can direct polarization state, functional roles and migration mode.[3] A continuum of M1-M2 polarization may arise even in the absence of polarizing cytokines and differences in substrate stiffness.[4] M1 macrophages were described as the pro-inflammatory type, important in direct host-defense against pathogens, such as phagocytosis and secretion of pro-inflammatory cytokines and microbicidal molecules. M2 macrophages were described to have quite the opposite function: regulation of the resolution phase of inflammation and the repair of damaged tissues. Later, more extensive in vitro and ex vivo studies have shown that macrophage phenotypes are much more diverse, overlapping with each other in terms of gene expression and function, revealing that these many hybrid states form a continuum of activation states which depend on the microenvironment.[5][6][7][8] Moreover, in vivo, there is a high diversity in gene expression profile between different populations of tissue macrophages.[9] Macrophage activation spectrum is thus considered to be wider, involving complex regulatory pathway to response to plethora of different signals from the environment.[10][11] The diversity of macrophage phenotypes still remain to be fully characterized in vivo.
The imbalance of the macrophage types is related to a number of immunity-related diseases.[12][13] For example, it has been shown that increased M1/M2 ratio correlates with development of inflammatory bowel disease,[14][15] as well as obesity in mice.[16][17][18] On the other side, in vitro experiments implicated M2 macrophages as the primary mediators of tissue fibrosis.[13] Several studies have associated the fibrotic profile of M2 macrophages with the pathogenesis of systemic sclerosis.[12][19]
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- ^ Mills CD, Kincaid K, Alt JM, Heilman MJ, Hill AM (June 2000). "M-1/M-2 macrophages and the Th1/Th2 paradigm". Journal of Immunology. 164 (12): 6166–73. doi:10.4049/jimmunol.164.12.6166. PMID 10843666.
- ^ Sridharan R, Cavanagh B, Cameron AR, Kelly DJ, O'Brien FJ (April 2019). "Material stiffness influences the polarization state, function and migration mode of macrophages". Acta Biomaterialia. 89: 47–59. doi:10.1016/j.actbio.2019.02.048. PMID 30826478. S2CID 73489194.
- ^ Specht H, Emmott E, Petelski AA, Huffman RG, Perlman DH, Serra M, et al. (January 2021). "Single-cell proteomic and transcriptomic analysis of macrophage heterogeneity using SCoPE2". Genome Biology. 22 (1): 50. doi:10.1186/s13059-021-02267-5. PMC 7839219. PMID 33504367.
- ^ Mosser DM, Edwards JP (December 2008). "Exploring the full spectrum of macrophage activation". Nature Reviews. Immunology. 8 (12): 958–69. doi:10.1038/nri2448. PMC 2724991. PMID 19029990.
- ^ Kreider T, Anthony RM, Urban JF, Gause WC (August 2007). "Alternatively activated macrophages in helminth infections". Current Opinion in Immunology. 19 (4): 448–53. doi:10.1016/j.coi.2007.07.002. PMC 2000338. PMID 17702561.
- ^ Rőszer T (2015). "Understanding the Mysterious M2 Macrophage through Activation Markers and Effector Mechanisms". Mediators of Inflammation. 2015: 816460. doi:10.1155/2015/816460. PMC 4452191. PMID 26089604.
- ^ Xue J, Schmidt SV, Sander J, Draffehn A, Krebs W, Quester I, et al. (February 2014). "Transcriptome-based network analysis reveals a spectrum model of human macrophage activation". Immunity. 40 (2): 274–88. doi:10.1016/j.immuni.2014.01.006. PMC 3991396. PMID 24530056.
- ^ Gautier EL, Shay T, Miller J, Greter M, Jakubzick C, Ivanov S, et al. (November 2012). "Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages". Nature Immunology. 13 (11): 1118–28. doi:10.1038/ni.2419. PMC 3558276. PMID 23023392.
- ^ Lavin Y, Winter D, Blecher-Gonen R, David E, Keren-Shaul H, Merad M, et al. (December 2014). "Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment". Cell. 159 (6): 1312–26. doi:10.1016/j.cell.2014.11.018. PMC 4437213. PMID 25480296.
- ^ Ginhoux F, Schultze JL, Murray PJ, Ochando J, Biswas SK (January 2016). "New insights into the multidimensional concept of macrophage ontogeny, activation and function". Nature Immunology. 17 (1): 34–40. doi:10.1038/ni.3324. PMID 26681460. S2CID 205370135.
- ^ a b Funes SC, Rios M, Escobar-Vera J, Kalergis AM (June 2018). "Implications of macrophage polarization in autoimmunity". Immunology. 154 (2): 186–195. doi:10.1111/imm.12910. PMC 5980179. PMID 29455468.
- ^ a b Wermuth PJ, Jimenez SA (2015). "The significance of macrophage polarization subtypes for animal models of tissue fibrosis and human fibrotic diseases". Clinical and Translational Medicine. 4: 2. doi:10.1186/s40169-015-0047-4. PMC 4384891. PMID 25852818.
- ^ Lissner D, Schumann M, Batra A, Kredel LI, Kühl AA, Erben U, May C, Schulzke JD, Siegmund B (June 2015). "Monocyte and M1 Macrophage-induced Barrier Defect Contributes to Chronic Intestinal Inflammation in IBD". Inflammatory Bowel Diseases. 21 (6): 1297–305. doi:10.1097/MIB.0000000000000384. PMC 4450953. PMID 25901973.
- ^ Zhu W, Yu J, Nie Y, Shi X, Liu Y, Li F, Zhang XL (2014). "Disequilibrium of M1 and M2 macrophages correlates with the development of experimental inflammatory bowel diseases". Immunological Investigations. 43 (7): 638–52. doi:10.3109/08820139.2014.909456. PMID 24921428. S2CID 9552010.
- ^ Lumeng CN, Bodzin JL, Saltiel AR (January 2007). "Obesity induces a phenotypic switch in adipose tissue macrophage polarization". The Journal of Clinical Investigation. 117 (1): 175–84. doi:10.1172/jci29881. PMC 1716210. PMID 17200717.
- ^ Ohashi K, Parker JL, Ouchi N, Higuchi A, Vita JA, Gokce N, et al. (February 2010). "Adiponectin promotes macrophage polarization toward an anti-inflammatory phenotype". The Journal of Biological Chemistry. 285 (9): 6153–60. doi:10.1074/jbc.m109.088708. PMC 2825410. PMID 20028977.
- ^ Cucak H, Grunnet LG, Rosendahl A (January 2014). "Accumulation of M1-like macrophages in type 2 diabetic islets is followed by a systemic shift in macrophage polarization". Journal of Leukocyte Biology. 95 (1): 149–60. doi:10.1189/jlb.0213075. PMID 24009176.
- ^ Soldano S, Contini P, Brizzolara R, Montagna P, Sulli A, Paolino S, Cutolo M (2015). "Increased presence of CD206+ macrophage subset in peripheral blood of systemic sclerosis patients". Annals of the Rheumatic Diseases. 74 (Supplement 1): A5–6. doi:10.1136/annrheumdis-2015-207259.13. S2CID 76272907.