A ROLE OF MACROPHAGES: AN OVERVIEW
The macrophage is a type of phagocytic cell, which is a type of cell those are responsible for detecting, engulfing and destroying pathogens and apoptotic cells. Macrophages are produced through the differentiation of monocytes, which turn into macrophages when they leave the blood. Macrophages also play a role in alerting the immune system to the presence of invaders. Macrophage lineage cells present a remarkably versatile array of functional specializations across vertebrates. As resident cells in virtually all tissues, macrophages aid in maintaining homeostatic environments, and upon infection, are typically one of the first cell types to encounter intruding pathogens, where they orchestrate appropriate immune responses. Another function of macrophages is to alert the immune system to microbial invasion. After ingesting a microbe, a macrophage presents a protein on its cell surface called an antigen, which signals the presence of the antigen to a corresponding T helper cell. Moreover macrophages might be a successful targeting site for targeted drug delivery approaches.
Keywords: macrophages, phagocytic cells, monocytes, immune system
2. Zhou, D.; Huang, C.; Lin, Z.; Zhan, S.; Kong, L.; Fang, C.; Li, J. Macrophage polarization and function with emphasis on the evolving roles of coordinated regulation of cellular signalling pathways. Cell. Signal. 2014, 26, 192â€“197.
3. North RJ. Cellular mediators of anti-Listeria immunity as an enlarged population of short lived, replicating T cells. Kinetics of their production. The Journal of experimental medicine. 1973; 138: 342-55.
4. Neumann, N.F.; Stafford, J.L.; Belosevic, M. Biochemical and functional characterisation of macrophage stimulating factors secreted by mitogen-induced goldfish kidney leucocytes. Fish Shellfish Immunol. 2000, 10, 167â€“186.
5. Rieger, A.M.; Hall, B.E.; Barreda, D.R. Macrophage activation differentially modulates particle binding, phagocytosis and downstream antimicrobial mechanisms. Dev. Comp. Immunol. 2010, 34, 1144â€“1159.
6. Grayfer, L.; Hodgkinson, J.W.; Belosevic, M. Antimicrobial responses of teleost phagocytes and innate immune evasion strategies of intracellular bacteria. Dev. Comp. Immunol. 2014, 43, 223â€“242.
7. Joerink, M.; Savelkoul, H.F.J.; Wiegertjes, G.F. Evolutionary conservation of alternative activation of macrophages: Structural and functional characterization of arginase 1 and 2 in carp (Cyprinus carpio L.). Mol. Immunol. 2006, 43, 1116â€“1128.
8. Takizawa, F.; Koppang, E.O.; Ohtani, M.; Nakanishi, T.; Hashimoto, K.; Fischer, U.; Dijkstra, J.M. Constitutive high expression of interleukin-4/13A and GATA-3 in gill and skin of salmonid fishes suggests that these tissues form Th2-skewed immune environments. Mol. Immunol. 2011, 48, 1360â€“1368.
9. Castro, R.; Zou, J.; Secombes, C.J.; Martin, S.A.M. Cortisol modulates the induction of inflammatory gene expression in a rainbow trout macrophage cell line. Fish Shellfish Immunol. 2011, 30, 215â€“223.
10. Grayfer, L.; Hodgkinson, J.W.; Hitchen, S.J.; Belosevic, M. Characterization and functional analysis of goldfish (Carassius auratus L.) interleukin-10. Mol. Immunol. 2011, 48, 563â€“571.
11. Joerink, M.; Forlenza, M.; Ribeiro, C.M.S.; de Vries, B.J.; Savelkoul, H.F.J.; Wiegertjes, G.F. Differential macrophage polarisation during parasitic infections in common carp (Cyprinus carpio L.). Fish Shellfish Immunol. 2006, 21, 561â€“571.
12. Gautier EL, et al. Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages. Nat Immunol. 2012; 13:1118â€“1128. [PubMed: 23023392].
13. Gordon S. Alternative activation of macrophages. Nat Rev Immunol. 2003; 3:23â€“35. [PubMed: 12511873]
14. Sica A, Mantovani A. Macrophage plasticity and polarization: in vivo veritas. The Journal of clinical investigation. 2012; 122:787â€“795. [PubMed: 22378047].
15. Geissmann F, et al. Development of monocytes, macrophages, and dendritic cells. Science. 2010; 327:656â€“661. [PubMed: 20133564].
16. Jenkins SJ, et al. Local Macrophage Proliferation, Rather than Recruitment from te Blood, Is a Sinature of Th2 Inflammation. Science. 2011.
17. Schulz C, et al. A lineage of myeloid cells independent of Myb and hematopoietic stem cells. Science. 2012; 336:86â€“90. [PubMed: 22442384].
18. Ohmori Y, Hamilton TA. IL-4-induced STAT6 suppresses IFN-gamma-stimulated STAT1-dependent transcription in mouse macrophages. The Journal of immunology. 1997; 159: 5474-82.
19. Satoh T, Takeuchi O, Vandenbon A, Yasuda K, Tanaka Y, Kamara Y, et al. The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminthic infection. Nature immunology. 2010; 11: 936-44. doi:10.1038/ni.1920.
20. Vishvakrama P, Sharma S. Liposomes: An Overview. Journal of Drug Delivery and Therapeutics, 2014; 0:47-55. doi:10.22270/jddt.v0i0.843
21. Oeckinghaus A, Hayden MS, Ghosh S. Crosstalk in NF-kappaB signalling pathways. Nature immunology. 2011; 12: 695-708. doi:10.1038/ni.2065.
22. Dwivedi C, Sahu R, Tiwari S, Satapathy T, Roy A. Role of liposome in novel drug delivery system. Journal of Drug Delivery and Therapeutics, 2014; 4(2):116-129. doi:10.22270/jddt.v4i2.768
23. Janssen, Knol, Egestion, Macrophages and hematopoietic cell clusters from mouse bone marrow. J exp med. 1985; 162(3):993â€“1014.
24. Dantzer r, oâ€™connor jc, freund gg, johnson rw, kelley kw. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat rev neurosci. 2008; 9(1):46â€“56.
25. Lawson LJ, Perry VH, Dri P, Gordon S. Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain. Neuroscience. 1990; 39(1):151â€“70
26. Kitamura T, Qian Bz, Pollard Jw. Immune Cell Promotion of Metastasis. Nat Rev Immunol. 2015; 15(2):73â€“86.
27. Abraham, D., Zins, K., Sioud, M., Lucas, T., SchaÂ¨ fer, R., Stanley, E.R., and Aharinejad, S. (2010). Stromal cell-derived CSF-1 blockade prolongs xenograft survival of CSF-1-negative neuroblastoma. Int. J. Cancer 126, 1339â€“1352.
28. Adeegbe, D.O., and Nishikawa, H. Natural and induced T regulatory cells in cancer. Frontiers in immunology 2013; 4, 190.
29. Balkwill, F., Charles, K.A., and Mantovani, A. Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell 2005; 7, 211â€“217.
30. Glasauer, S.M.K.; Neuhauss, S.C.F. Whole-genome duplication in teleost fishes and its evolutionary consequences. Mol. Genet. Genom. 2014, 289, 1045â€“1060.
31. Coussens, L.M., and Werb, Z. 2002. Inflammation and cancer. Nature 420:860- 867.
32. Pollard, J.W. 2004. Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer 4:71-78.
33. Mantovani, A., Sozzani, S., Locati, M., Allavena, P., and Sica, A. 2002. Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol 23:549-555.
34. Grivennikov, S.I., Greten, F.R., and Karin, M. 2010. Immunity, inflammation, and cancer. Cell 140:883-899.
35. Van Ravenswaay Claasen, H.H., Kluin, P.M., and Fleuren, G.J. 1992. Tumor infiltrating cells in human cancer. On the possible role of CD16+ macrophages in antitumor cytotoxicity. Lab Invest 67:166-174.
36. Karin, M., and Greten, F.R. 2005. NF-kappa B: linking inflammation and immunity to cancer development and progression. In Nat Rev Immunol. England. 749-759.
37. Qian, B.Z., and Pollard, J.W. 2010. Macrophage diversity enhances tumor progression and metastasis. In Cell. United States: 2010 Elsevier Inc. 39-51.
38. Wyckoff, J.B., Wang, Y., Lin, E.Y., Li, J.F., Goswami, S., Stanley, E.R., Segall, J.E., Pollard, J.W., and Condeelis, J. 2007. Direct visualization of macrophageassisted tumor cell intravasation in mammary tumors. In Cancer Res. United States. 2649-2656.
39. Alam, M., and Ratner, D. 2001. Cutaneous squamous-cell carcinoma. N Engl J Med 344:975-983. 10. Lomas, A., Leonardi-Bee, J., and Bath-Hextall, F. 2012.
40. A systematic review of worldwide incidence of nonmelanoma skin cancer. Br J Dermatol 166:1069- 1080.
41. Neville, J.A., Welch, E., and Leffell, D.J. 2007. Management of nonmelanoma skin cancer in 2007. In Nat Clin Pract Oncol. England. 462-469
42. Criscione VD, Weinstock MA, Naylor MF, Luque C, Eide MJ, Bingham SF, Department of Veteran Affairs Topical Tretinoin Chemoprevention Trial G, Actinic keratoses: natural history and risk of malignant transformation in the Veterans Affairs Topical Tretinoin Chemoprevention Trial. Cancer 2009; 115: 2523â€“2530.
43. Chen YG, Wang Q, Lin SL, Chang CD, Chuang J, Ying SY, Activin signaling and its role in regulation of cell proliferation, apoptosis, and carcinogenesis. Exp Biol Med (Maywood) 2006; 231: 534â€“544.
44. Antsiferova M, Huber M, Meyer M, Czuchra A, Ramadan T, MacLeod AS, HavranWL, Dummer R, Hohl D, Werner S, Activin enhances skin tumourigenesis and malignant progression by inducing a proâ€tumourigenic immune cell response. Nat Commun 2011; 2: 576.
45. Antsiferova M, Werner S, the bright and the dark sides of activin in wound healing and cancer. J Cell Sci 2012; 125: 3929â€“3937
46. Arwert EN, Lal R, Quist S, Rosewell I, van Rooijen N, Watt FM, Tumor formation initiated by nondividing epidermal cells via an inflammatory infiltrate. Proc Malt Acad Sci USA 2010; 107: 19903â€“19908
47. Basile JR, Holmbeck K, Bugge TH, Gutkind JS, MT1â€MMP controls tumorâ€induced angiogenesis through the release of semaphorin 4D. J Biol Chem 2007; 282: 6899â€“6905
48. Bolger AM, Lohse M, Usadel B, Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30: 2114.
49. Musawi SL, Kelly EK, Qian H, La M, Lu L, Lovrecz G, Ziemann M, Lazarus R et al, Development of novel activinâ€ targeted therapeutics. Mol Ther 2015; 23:434â€“444
50. Daniel D, Meyer Morse N, Bergsland EK, Dehne K, Coussens LM, Hanahan D, Immune enhancement of skin carcinogenesis by CD4+ T cells. J Exp Med 2003; 197: 1017â€“1028.
51. .Egeblad M, Nakasone ES, Werb Z. Tumors as organs: complex tissues that interface with the entire organism. Dev Cell 2010; 18:884â€“901.
52. Elinav E, Nowarski R, Thaiss CA, Hu B, Jin C, Flavell RA. Inflammationinduced cancer: crosstalk between tumours, immune cells and microorganisms. Nat Rev Cancer 2013; 13:759â€“71.
53. Pietras K, Ostman A. Hallmarks of cancer: interactions with the tumor stroma. Exp Cell Res 2010; 316:1324â€“31.
54. Barcellos-Hoff MH, Lyden D, Wang TC. The evolution of the cancer niche during multistage carcinogenesis. Nat Rev Cancer 2013; 13:511â€“8.
55. Arwert EN, Hoste E, Watt FM. Epithelial stem cells, wound healing and cancer. Nat Rev Cancer 2012; 12:170â€“80.
56. Arwert EN, Lal R, Quist S, Rosewell I, van Rooijen N, Watt FM. Tumor formation initiated by nondividing epidermal cells via an inflammatory infiltrate. Proc Natl Acad Sci U S A 2010; 107:19903â€“8.
57. Hobbs RM, Silva-Vargas V, Groves R, Watt FM. Expression of activated MEK1 in differentiating epidermal cells is sufficient to generate hyperproliferative and inflammatory skin lesions. J Invest Dermatol 2004; 123:503â€“15.
58. Pollard JW. Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer 2004; 4:71â€“8.
59. Balkwill F, Charles KA, Mantovani A. Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell 2005; 7:211â€“7.
60. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell 2010; 140:883â€“99.
61. North RJ. Cellular mediators of anti-Listeria immunity as an enlarged population of short lived, replicating T cells. Kinetics of their production. The Journal of experimental medicine. 1973; 138: 342-55.
62. David JR. Lymphocyte mediators and cellular hypersensitivity. The New England journal of medicine. 1973; 288: 143-9. Doi: 10.1056/NEJM197301182880311.
63. Nathan CF, Murray HW, Wiebe ME, Rubin BY. Identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. The Journal of experimental medicine. 1983; 158: 670-89.
64. Mosmann TR, Coffman RL. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annual review of immunology. 1989; 7: 145-73. doi:10.1146/annurev.iy.07.040189.001045.
65. Abramson SL, Gallin JI. IL-4 inhibits superoxide production by human mononuclear phagocytes. The Journal of immunology. 1990; 144: 625-30.
66. Stein M, Keshav S, Harris N, Gordon S. Interleukin 4 potently enhances murine macrophage mannose receptor activity: a marker of alternative immunologic macrophage activation. The Journal of experimental medicine.1992; 176: 287-92.
67. Moore KJ, Tabas I. Macrophages in the pathogenesis of atherosclerosis. Cell. 2011; 145: 341-55. doi:10.1016/j.cell.2011.04.005.
68. Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, and De Simone G, et al. Executive summary: heart disease and stroke statistics--2010 update: a report from the American Heart Association. Circulation. 2010; 121: 948-54.
69. Swirski FK, Nahrendorf M. Leukocyte behavior in atherosclerosis, myocardial infarction, and heart failure. Science. 2013; 339: 161-6. doi:10.1126/science.1230719.
70. Fuster JJ, Fernandez P, Gonzalez-Navarro H, Silvestre C, Nabah YN, Andres V. Control of cell proliferation in atherosclerosis: insights from animal models and human studies. Cardiovascular research. 2010; 86: 254-64. doi:10.1093/cvr/cvp363.
71. Mestas J, Ley K. Monocyte-endothelial cell interactions in the development of atherosclerosis. Trends in cardiovascular medicine. 2008; 18: 228-32.doi:10.1016/j.tcm.2008.11.004.
72. Kirbis S, Breskvar UD, Sabovic M, Zupan I, Sinkovic A. Inflammation markers in patients with coronary artery disease--comparison of intracoronary and systemic levels. Wiener klinische Wochenschrift. 2010; 122 Suppl 2: 31-4. Doi: 10.1007/s00508-010-1343-z.
73. Khallou-Laschet J, Varthaman A, Fornasa G, Compain C, Gaston AT, Clement M, et al. Macrophage plasticity in experimental atherosclerosis. PloS one. 2010; 5: e8852. doi:10.1371/journal.pone.0008852.
74. Tsimikas S, Miller YI. Oxidative modification of lipoproteins: mechanisms, role in inflammation and potential clinical applications in cardiovascular disease. Current pharmaceutical design. 2011; 17: 27-37
75. Handberg A, Skjelland M, Michelsen AE, Sagen EL, Krohg-Sorensen K, Russell D, et al. Soluble CD36 in plasma is increased in patients with symptomatic atherosclerotic carotid plaques and is related to plaque instability. Stroke, a journal of cerebral circulation. 2008; 39: 3092-5. doi:10.1161/STROKEAHA.108.517128.
76. Huo Y, Zhao L, Hyman MC, Shashkin P, Harry BL, Burcin T, et al. Critical role of macrophage 12/15-lipoxygenase for atherosclerosis in apolipoprotein E-deficient mice. Circulation. 2004; 110: 2024-31. doi:10.1161/01.CIR.0000143628.37680.F6.
77. Thorp E, Tabas I. Mechanisms and consequences of efferocytosis in advanced atherosclerosis. Journal of leukocyte biology. 2009; 86: 1089-95. doi:10.1189/jlb.0209115.
78. Olshansky SJ, Passaro DJ, Hershow RC, Layden J, Carnes BA, Brody J, et al. A potential decline in life expectancy in the United States in the 21st century. The New England journal of medicine. 2005; 352: 1138-45. Doi: 10.1056/NEJMsr043743.
79. Nguyen KD, Qiu Y, Cui X, Goh YP, Mwangi J, David T, et al. alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis. Nature. 2011; 480: 104-8. Doi: 10.1038/nature10653.
80. Mantovani A. Cancer: Inflaming metastasis. Nature. 2009; 457: 36-7. Doi: 10.1038/457036b.
81. Wei Q, Fang W, Ye L, Shen L, Zhang X, Fei X, et al. Density of tumor associated macrophage correlates with lymph node metastasis in papillary thyroid carcinoma. Thyroid: official journal of the American Thyroid Association. 2012. doi:10.1089/thy.2011-0452.
82. Shirabe K, Mano Y, Muto J, Matono R, Motomura T, Toshima T, et al. Role of tumor-associated macrophages in the progression of hepatocellular carcinoma. Surgery today. 2012; 42: 1-7. Doi: 10.1007/s00595-011-0058-8.
83. Gocheva V, Wang HW, Gadea BB, Shree T, Hunter KE, Garfall AL, et al. IL-4 induces cathepsin protease activity in tumor-associated macrophages to promote cancer growth and invasion. Genes & development. 2010; 24: 241-55. doi:10.1101/gad.1874010
84. Kitamura T, Kometani K, Hashida H, Matsunaga A, Miyoshi H, Hosogi H, et al. SMAD4-deficient intestinal tumors recruit CCR1+ myeloid cells that promote invasion. Nature genetics. 2007; 39: 467-75. Doi: 10.1038/ng1997.
85. Moreira AP, Hogaboam CM. Macrophages in allergic asthma: fine-tuning their pro- and anti-inflammatory actions for disease resolution. Journal of interferon & cytokine research: the official journal of the International Society for Interferon and Cytokine Research. 2011; 31: 485-91. doi:10.1089/jir.2011.0027.
86. Kim YK, Oh SY, Jeon SG, Park HW, Lee SY, Chun EY, et al. Airway exposure levels of lipopolysaccharide determine type 1 versus type 2 experimental asthma. The Journal of immunology. 2007; 178: 5375-82.
87. Naura AS, Zerfaoui M, Kim H, Abd Elmageed ZY, Rodriguez PC, Hans CP, et al. Requirement for inducible nitric oxide synthase in chronic allergen exposure-induced pulmonary fibrosis but not inflammation. The Journal of immunology. 2010; 185: 3076-85. doi:10.4049/jimmunol.0904214.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (SeeÂ The Effect of Open Access).