Migration, proliferation and cell death of regenerating liver macrophages in an experimental model
- Authors: Grinberg M.V.1, Lokhonina A.V.2, Vishnyakova P.A.2, Makarov A.V.3, Kananykhina E.Y.4, Eremina I.Z.1, Glinkina V.V.3, Elchaninov A.V.4, Fatkhudinov T.K.4
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Affiliations:
- RUDN University
- National Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician V.I. Kulakov of Ministry of Healthcare of Russian Federation
- Pirogov Russian National Research Medical University, Ministry of Healthcare of the Russian Federation
- Avtsyn Research Institute of Human Morphology of Federal state budgetary scientific institution «Petrovsky National Research Centre of Surgery»
- Issue: Vol 27, No 4 (2023): PHYSIOLOGY. EXPERIMENTAL PHYSIOLOGY
- Pages: 449-458
- Section: PHYSIOLOGY. EXPERIMENTAL PHYSIOLOGY
- URL: https://journal-vniispk.ru/2313-0245/article/view/319695
- DOI: https://doi.org/10.22363/2313-0245-2023-27-4-449-458
- EDN: https://elibrary.ru/JDEJXS
- ID: 319695
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Abstract
Relevance . Macrophages are the leading regulatory cell-lineage taking part in reparative processes in mammals, and the liver is no exception. The ratio of monocyte migration, proliferation and death of macrophages during liver regeneration requires further studies. The aim was to quantify the intensity of monocyte migration, cell proliferation and apoptosis of resident liver macrophages after its 70 % resection in a mouse model. Materials and Methods. We performed 70 % liver resection in sexually mature male BalbC mice. Cells of liver monocyte-macrophage system were obtained by magnetic sorting by marker F4/80. The immunophenotype of the isolated cells was further studied by cytofluorimetry, the level of proliferation and cell death, the content of cyclins and P53 was determined by western blot. Results and Discussion . It was found that after partial hepatectomy there is a marked migration of monocytes/macrophages positive for Ly6C and CD11b markers to the liver, the migration process starts already in the first day after the operation. On the same terms there is a rise in proliferative activity of macrophages, established by Ki67 marker, the peak of proliferation - 3 days after partial hepatectomy. A significant increase in the number of dying macrophages was found early after liver resection. Conclusion . The obtained data indicate that liver regeneration in mammals on the model in mice is accompanied by proliferation migration and cell death of macrophages. Taking into account the immunophenotype of macrophages, we can conclude that Ly6C+ blood monocytes migrate to the liver, and resident macrophages participate in proliferation. The obtained data confirm the universality of the course of reparative processes in mammals.
Keywords
About the authors
Maria V. Grinberg
RUDN University
Email: elchandrey@yandex.ru
ORCID iD: 0000-0002-9159-4232
SPIN-code: 6260-1863
Moscow, Russian Federation
Anastasia V. Lokhonina
National Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician V.I. Kulakov of Ministry of Healthcare of Russian Federation
Email: elchandrey@yandex.ru
ORCID iD: 0000-0001-8077-2307
SPIN-code: 4521-2250
Moscow, Russian Federation
Polina A. Vishnyakova
National Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician V.I. Kulakov of Ministry of Healthcare of Russian Federation
Email: elchandrey@yandex.ru
ORCID iD: 0000-0001-8650-8240
SPIN-code: 3406-3866
Moscow, Russian Federation
Andrey V. Makarov
Pirogov Russian National Research Medical University, Ministry of Healthcare of the Russian Federation
Email: elchandrey@yandex.ru
ORCID iD: 0000-0003-2133-2293
SPIN-code: 3534-3764
Moscow, Russian Federation
Eugenia Yu. Kananykhina
Avtsyn Research Institute of Human Morphology of Federal state budgetary scientific institution «Petrovsky National Research Centre of Surgery»
Email: elchandrey@yandex.ru
ORCID iD: 0000-0002-9779-2918
SPIN-code: 8256-5754
Moscow, Russian Federation
Irina Z. Eremina
RUDN University
Email: elchandrey@yandex.ru
ORCID iD: 0000-0001-5444-9231
SPIN-code: 5819-6159
Moscow, Russian Federation
Valeria V. Glinkina
Pirogov Russian National Research Medical University, Ministry of Healthcare of the Russian Federation
Email: elchandrey@yandex.ru
ORCID iD: 0000-0001-8708-6940
SPIN-code: 4425-5052
Moscow, Russian Federation
Andrey V. Elchaninov
Avtsyn Research Institute of Human Morphology of Federal state budgetary scientific institution «Petrovsky National Research Centre of Surgery»
Author for correspondence.
Email: elchandrey@yandex.ru
ORCID iD: 0000-0002-2392-4439
SPIN-code: 5160-9029
Moscow, Russian Federation
Timur Kh. Fatkhudinov
Avtsyn Research Institute of Human Morphology of Federal state budgetary scientific institution «Petrovsky National Research Centre of Surgery»
Email: elchandrey@yandex.ru
ORCID iD: 0000-0002-6498-5764
SPIN-code: 7919-8430
Moscow, Russian Federation
References
- Slack JM. Animal regeneration: ancestral character or evolutionary novelty? EMBO Rep. 2017;18(9):1497-1508. doi: 10.15252/embr.201643795
- Brockes JP, Kumar A. Comparative Aspects of Animal Regeneration. Annu Rev Cell Dev Biol. 2008;24(1):525-549. doi: 10.1146/annurev.cellbio.24.110707.175336
- Muneoka K, Dawson LA. Evolution of epimorphosis in mammals. J Exp Zool Part B Mol Dev Evol. Published online January 17, 2020: jez.b.22925. doi: 10.1002/jez.b.22925
- Mescher AL, Neff AW, King MW. Inflammation and immunity in organ regeneration. Dev Comp Immunol. 2017;66:98-110. doi: 10.1016/j.dci.2016.02.015
- Iismaa SE, Kaidonis X, Nicks AM, Bogush N, Kikuchi K, Naqvi N, Harvey R, Husain A, Graham R. Comparative regenerative mechanisms across different mammalian tissues. npj Regen Med. 2018;3(1). doi: 10.1038/s41536-018-0044-5
- Bangru S, Kalsotra A. Cellular and molecular basis of liver regeneration. Semin Cell Dev Biol. 2020;100:74-87. doi: 10.1016/j.semcdb.2019.12.004
- Elchaninov AV, Fatkhudinov TK, Vishnyakova PA, Lokhonina AV, Sukhikh GT. Phenotypical and Functional Polymorphism of Liver Resident Macrophages. Cells. 2019;8(9). doi: 10.3390/cells8091032
- Zigmond E, Samia-Grinberg S, Pasmanik-Chor M, Brazowski E, Shibolet O, Halpern Z, Varol C. Infiltrating Monocyte-Derived Macrophages and Resident Kupffer Cells Display Different Ontogeny and Functions in Acute Liver Injury. J Immunol. 2014;193(1):344-353. doi: 10.4049/jimmunol.1400574
- You Q, Holt M, Yin H, Li G, Hu CJ, Ju C. Role of hepatic resident and infiltrating macrophages in liver repair after acute injury. Biochem Pharmacol. 2013;86(6):836-843. doi:10.1016/j. bcp.2013.07.006
- Michalopoulos GK. Advances in liver regeneration. Expert Rev Gastroenterol Hepatol. 2014;8(8):897-907. doi: 10.1586/17474124.2014.934358
- Elchaninov AV, Fatkhudinov TK, Usman NY, Kananykhina EY, Arutyunyan IV., Makarov AV, Lokhonina AV, Eremina IZ, Surovtsev VV, Goldshtein DV, Bolshakova GB, Glinkina VV, Sukhikh GT. Dynamics of macrophage populations of the liver after subtotal hepatectomy in rats. BMC Immunol. 2018;19(1):23. doi: 10.1186/s12865-018-0260-1
- Song Z, Humar B, Gupta A, Maurizio E, Borgeaud N, Graf R, Clavien PA, Tian Y. Exogenous melatonin protects small-for-size liver grafts by promoting monocyte infiltration and releases interleukin-6. J Pineal Res. 2018;65(1): e12486. doi: 10.1111/jpi.12486
- Michalopoulos GK. Liver regeneration: alternative epithelial pathways. Int J Biochem Cell Biol. 2011;43(2):173-179. doi: 10.1016/j.biocel.2009.09.014
- Nishiyama K, Nakashima H, Ikarashi M, Kinoshita M, Nakashima M, Aosasa S, Seki S, Yamamoto J. Mouse CD11b+Kupffer cells recruited from bone marrow accelerate liver regeneration after partial hepatectomy. PLoS One. 2015;10(9):1-16. doi: 10.1371/journal.pone.0136774
- Danilova IG, Yushkov BG, Kazakova IA, Belousova A V., Minin AS, Abidov MT. Recruitment of macrophages and bone marrow stem cells to regenerating liver promoted by sodium phthalhydrazide in mice. Biomed Pharmacother. 2019;110:594-601. doi: 10.1016/j.biopha.2018.07.086
- Nevzorova Y, Tolba R, Trautwein C, Liedtke C. Partial hepatectomy in mice. Lab Anim. 2015;49(1_suppl):81-88. doi: 10.1177/0023677215572000
- Eming SA, Hammerschmidt M, Krieg T, Roers A. Interrelation of immunity and tissue repair or regeneration. Semin Cell Dev Biol. 2009;20(5):517-527. doi: 10.1016/j.semcdb.2009.04.009
- Kinoshita M, Uchida T, Sato A, Nakashima M, Nakashima H, Shono S, Habu Y, Miyazaki H, Hiroi S, Seki S. Characterization of two F4/80-positive Kupffer cell subsets by their function and phenotype in mice. J Hepatol. 2010;53(5):903-910. doi: 10.1016/j.jhep.2010.04.037
- Goh YP, Henderson NC, Heredia JE, Red Eagle A, Odegaard JI, Lehwald N, Nguyen KD, Sheppard D, Mukundan L, Locksley RM, Chawla A. Eosinophils secrete IL-4 to facilitate liver regeneration. Proc. Natl. Acad. Sci. U.S.A. 2013;110(24): 9914-9919. doi: 10.1073/pnas.1304046110
- Jenkins SJ, Ruckerl D, Cook PC, Jones LH, Finkelman FD, van Rooijen N, MacDonald AS, Allen JE. Local macrophage proliferation, rather than recruitment from the blood, is a signature of T H2 inflammation. Science. 2011;332(6035):1284-1288. doi: 10.1126/science.1204351
- Michalopoulos GK, DeFrances MC. Liver Regeneration. Science. 1997;276(5309):60-66. doi: 10.1126/science.276.5309.60
- Zou Y, Bao Q, Kumar S, Hu M, Wang GY, Dai G. Four waves of hepatocyte proliferation linked with three waves of hepatic fat accumulation during partial hepatectomy-induced liver regeneration. PLoS One. 2012;7(2): e30675. doi: 10.1371/journal.pone.0030675
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