Bağışıklık Sisteminin Bekçileri Makrofajların Gizemli Dünyası

Öz

Mononükleer fagositik sistemin önemli elemanları olan makrofajlar vücudun savunma mekanizmalarının sürdürülmesi için önemlidirler. Güçlü fagositik aktiviteleri ve verimli antijen sunumlarıyla tanınan bu çok yönlü hücreler, etkilerini bağışıklığın ötesine taşıyarak doku gelişimi, onarımı ve homeostazisinde önemli roller oynarlar. Oldukça heterojen bir grup olan makrofajlar, farklı dokuların özel ihtiyaçlarına uyum sağlayarak çeşitli organlarda farklı isimler alırlar. İki ana fenotipe ayrılabilirler: klasik olarak aktive edilmiş (pro-inflamatuar) makrofajlar ve alternatif olarak aktive edilmiş (anti-inflamatuar) makrofajlar. Makrofaj polarizasyonunu kontrol ederek inflamatuar yanıtları düzenlemek makrofajlarla bağlantılı birçok hastalığın engellenmesinde ve tedavisinde etkili olabilir. Bu derlemede makrofajların kökenleri, mikroskobik ve fonksiyonel özellikleri, tipleri, işaretleme yöntemleri ve klinik önemleri ele alınmıştır.

Anahtar Kelimeler

• fenotip
• inflamasyon
• Makrofaj

The Mysterious World of Macrophages, the Guardians of the Immune System

Öz

Macrophages, key players of the mononuclear phagocytic system, are essential for maintaining the body’s defense mechanisms. Renowned for their robust phagocytic activity and efficient antigen presentation, these versatile cells extend their influence beyond immunity, playing pivotal roles in tissue development, repair, and homeostasis. As a highly heterogeneous group, macrophages adapt to the specific needs of different tissues, earning distinct names across various organs. They can polarize into two major phenotypes: classically activated (pro-inflammatory) macrophages and alternatively activated (anti-inflammatory) macrophages. Regulating inflammatory responses by controlling macrophage polarization may be effective in preventing and treating many diseases associated with macrophages. In this review, the origins, microscopic and functional properties, types, labeling methods and clinical importance of macrophages are discussed.

Anahtar Kelimeler

• phenotype
• inflammation
• Macrophages

Kaynakça

1. Kloc M, Kubiak JZ. The role of monocytes and macrophages in homeostasis and disease and novel avenues for putative treatments. International Journal of Molecular Sciences. 2021;22(9):4927.
2. Mass E, Lachmann N. From macrophage biology to macrophage-based cellular immunotherapies. Gene Therapy. 2021;28(9):473-476.
3. Eşrefoğlu M. Genel Histoloji. Geliştirilmiş 3. baskı. İstanbul: İstanbul Tıp Kitabevleri; 2021. 350 p.
4. Parasar P, Guru N, Nayak N. Contribution of macrophages to fetomaternal immunological tolerance. Human Immunology. 2021;82(5):325-331.
5. Strizova Z, Benesova I, Bartolini R, Novysedlak R, Cecrdlova E, Foley LK, et al. M1/M2 macrophages and their overlaps–myth or reality? Clinical Science (London, England : 1979). 2023;137(15):1067-1093.
6. Wang Y, Smith W, Hao D, He B, Kong L. M1 and M2 macrophage polarization and potentially therapeutic naturally occurring compounds. International Immunopharmacology. 2019;70:459-466.
7. Kumar V. Introductory chapter: Macrophages–More than sentinel innate immune cells. In: Kumar V, editors. Macrophages-celebrating 140 years of discovery. London: IntechOpen; 2022. p. 1-14.
8. Gordon S. Elie Metchnikoff, the man and the myth. Journal of Innate Immunity. 2016;8(3):223-227.

9. Mosser DM, Hamidzadeh K, Goncalves R. Macrophages and the maintenance of homeostasis. Cellular & Molecular Immunology. 2021;18(3):579-587.
10. Rasmussen N. Rene Dubos, the autochthonous flora, and the discovery of the microbiome. Journal of the History of Biology. 2022;55(3):537-558.
11. Furth VR, Cohn ZA. The origin and kinetics of mononuclear phagocytes. The Journal of Experimental Medicine. 1968;128(3):415-435.
12. Ginhoux F, Greter M, Leboeuf M, Nandi S, See P, Gokhan S, et al. Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science (New York, N.Y.). 2010;330(6005):841-845.
13. Schulz C, Perdiguero EG, Chorro L, Szabo-Rogers H, Cagnard N, Kierdorf K, et al. A lineage of myeloid cells independent of Myb and hematopoietic stem cells. Science (New York, N.Y.). 2012;336(6077):86-90.
14. Yona S, Kim KW, Wolf Y, Mildner A, Varol D, Breker M, et al. Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis. Immunity. 2013;38(1):79-91.
15. Steinman RM, Moberg CL. Zanvil Alexander Cohn 1926-1993. The Journal of Experimental Medicine. 1994;179(1):1-30.
16. Gordon S. The macrophage: past, present and future. European Journal of Immunology. 2007;37(S1):S9-S17.
17. Shapouri‐Moghaddam A, Mohammadian S, Vazini H, Taghadosi M, Esmaeili SA, Mardani F, et al. Macrophage plasticity, polarization, and function in health and disease. Journal of Cellular Physiology. 2018;233(9):6425-6440.
18. Lendeckel U, Venz S, Wolke C. Macrophages: Shapes and functions. ChemTexts. 2022;8(2):12.
19. Wynn TA, Chawla A, Pollard JW. Macrophage biology in development, homeostasis and disease. Nature. 2013;496(7446):445-455.
20. Maheshwari A. Innate immune memory in macrophages. Newborn (Clarksville, Md). 2023;2(1):60-79.
21. Sorenson RL, Brelje TC. Atlas of human histology: A guide to microscopic structure of cells, tissues and organs. 3th ed. Minnesota: University of Minnesota Bookstore; 2014. 367 p.
22. Yan J, Horng T. Lipid metabolism in regulation of macrophage functions. Trends in Cell Biology. 2020;30(12):979-989.
23. Duong L, Radley H, Lee B, Dye D, Pixley F, Grounds M, et al. Macrophage function in the elderly and impact on injury repair and cancer. Immunity & Ageing. 2021;18(1):4.
24. Gordon S, Plüddemann A. Tissue macrophages: heterogeneity and functions. BMC Biology. 2017;15(1):53.
25. Locati M, Curtale G, Mantovani A. Diversity, mechanisms, and significance of macrophage plasticity. Annual Review of Pathology: Mechanisms of Disease. 2020;15:123-147.
26. Hirayama D, Iida T, Nakase H. The phagocytic function of macrophage-enforcing innate immunity and tissue homeostasis. International Journal of Molecular Sciences. 2017;19(1):92.
27. Gordon S, Taylor PR. Monocyte and macrophage heterogeneity. Nature Reviews Immunology. 2005;5(12):953-964.
28. Odegaard JI, Chawla A. Pleiotropic actions of insulin resistance and inflammation in metabolic homeostasis. Science (New York, N.Y.). 2013;339(6116):172-177.
29. Sun K, Kusminski CM, Scherer PE. Adipose tissue remodeling and obesity. The Journal of Clinical Investigation. 2011;121(6):2094-2101.
30. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW. Obesity is associated with macrophage accumulation in adipose tissue. The Journal of Clinical Investigation. 2003;112(12):1796-1808.
31. Samuel VT, Shulman GI. Mechanisms for insulin resistance: common threads and missing links. Cell. 2012;148(5):852-871.
32. Pollard JW. Trophic macrophages in development and disease. Nature Reviews Immunology. 2009;9(4):259-270.
33. Erblich B, Zhu L, Etgen AM, Dobrenis K, Pollard JW. Absence of colony stimulation factor-1 receptor results in loss of microglia, disrupted brain development and olfactory deficits. Plos One. 2011;6(10):e26317.
34. Stefater JA, Ren S, Lang RA, Duffield JS. Metchnikoff's policemen: macrophages in development, homeostasis and regeneration. Trends in Molecular Medicine. 2011;17(12):743-752.
35. Fantin A, Vieira JM, Gestri G, Denti L, Schwarz Q, Prykhozhij S, et al. Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of VEGF-mediated endothelial tip cell induction. Blood, The Journal of the American Society of Hematology. 2010;116(5):829-840.
36. Kawane K, Fukuyama H, Kondoh G, Takeda J, Ohsawa Y, Uchiyama Y, et al. Requirement of DNase II for definitive erythropoiesis in the mouse fetal liver. Science (New York, N.Y.). 2001;292(5521):1546-1549.
37. Kloc M, Ghobrial RM, Wosik J, Lewicka A, Lewicki S, Kubiak JZ. Macrophage functions in wound healing. Journal of Tissue Engineering and Regenerative Medicine. 2019;13(1):99-109.
38. Murray PJ, Wynn TA. Protective and pathogenic functions of macrophage subsets. Nature Reviews Immunology. 2011;11(11):723-37.
39. Zhang C, Yang M, Ericsson A. Function of macrophages in disease: current understanding on molecular mechanisms. Frontiers in Immunology. 2021;12:620510.
40. Yunna C, Mengru H, Lei W, Weidong C. Macrophage M1/M2 polarization. European Journal of Pharmacology. 2020;877:173090.
41. Li P, Ma C, Li J, You S, Dang L, Wu J, et al. Proteomic characterization of four subtypes of M2 macrophages derived from human THP-1 cells. Journal of Zhejiang University-Science B. 2022;23(5):407-422.
42. Gharavi AT, Hanjani NA, Movahed E, Doroudian M. The role of macrophage subtypes and exosomes in immunomodulation. Cellular & Molecular Biology Letters. 2022;27(1):83.
43. Wei Q, Deng Y, Yang Q, Zhan A, Wang L. The markers to delineate different phenotypes of macrophages related to metabolic disorders. Frontiers in Immunology. 2023;14:1084636.
44. Nikovics K, Favier AL. Macrophage Identification In Situ. Biomedicines. 2021;9(10):1393.
45. Kosmac K, Peck BD, Walton RG, Mula J, Kern PA, Bamman MM, et al. Immunohistochemical identification of human skeletal muscle macrophages. Bio-protocol. 2018;8(12):e2883.
46. Rhein P, Mitlohner R, Basso G, Gaipa G, Dworzak MN, Kirschner-Schwabe R, et al. CD11b is a therapy resistance–and minimal residual disease–specific marker in precursor B-cell acute lymphoblastic leukemia. Blood, The Journal of the American Society of Hematology. 2010;115(18):3763-3771.
47. Sica A, Mantovani A. Macrophage plasticity and polarization: in vivo veritas. The Journal of Clinical Investigation. 2012;122(3):787-795.
48. Qian B-Z, Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell. 2010;141(1):39-51.
49. Xu Y, Wang X, Liu L, Wang J, Wu J, Sun C. Role of macrophages in tumor progression and therapy. International Journal of Oncology. 2022;60(5):57.
50. Yang S, Zhao M, Jia S. Macrophage: key player in the pathogenesis of autoimmune diseases. Frontiers in Immunology. 2023;14:1080310.
51. Ardura JA, Rackov G, Izquierdo E, Alonso V, Gortazar AR, Escribese MM. Targeting macrophages: friends or foes in disease? Frontiers in Pharmacology. 2019;10:1255.
52. Wu J, He S, Song Z, Chen S, Lin X, Sun H, et al. Macrophage polarization states in atherosclerosis. Frontiers in Immunology. 2023;14:1185587.
53. Eshghjoo S, Kim DM, Jayaraman A, Sun Y, Alaniz RC. Macrophage polarization in atherosclerosis. Genes. 2022;13(5):756.
54. Bowdish DM, Gordon S. Macrophage function disorders. Encyclopedia of Life Sciences Chichester, UK: John Wiley & Sons, Ltd. 2009:1-12.
55. Hou P, Fang J, Liu Z, Shi Y, Agostini M, Bernassola F, et al. Macrophage polarization and metabolism in atherosclerosis. Cell Death & Disease. 2023;14(10):691.
56. Hu M, Yao Z, Xu L, Peng M, Deng G, Liu L, et al. M2 macrophage polarization in systemic sclerosis fibrosis: pathogenic mechanisms and therapeutic effects. Heliyon. 2023;9(5):e16206.
57. Al-Adwi Y, Westra J, Van Goor H, Burgess JK, Denton CP, Mulder DJ. Macrophages as determinants and regulators of fibrosis in systemic sclerosis. Rheumatology (Oxford, England). 2023;62(2):535-545.
58. Lv J, Wang Z, Qu Y, Zhu H, Zhu Q, Tong W, et al. Distinct uptake, amplification, and release of SARS-CoV-2 by M1 and M2 alveolar macrophages. Cell Discovery. 2021;7(1):24.
59. Knoll R, Schultze JL, Schulte-Schrepping J. Monocytes and Macrophages in COVID-19. Frontiers in Immunology. 2021;12:720109.
60. Lee J-W, Chun W, Lee HJ, Min J-H, Kim S-M, Seo J-Y, et al. The role of macrophages in the development of acute and chronic inflammatory lung diseases. Cells. 2021;10(4):897.