THE TYPES OF PROGRAMMED HEPATOCYTE DEATH IN CHRONIC HEPATITIS C
Abstract
Background. Basically, there are two mechanisms of hepatocyte death in liver damage: non-programmed and programmed. The most studied and widely represented in the illustrations are the changes in the liver associated with unprogrammed hepatocyte death. Visualization of the main types of programmed hepatocyte death is lacking. Objective. To present morphological characteristics of the main subprograms of hepatocyte death according to light and electron microscopy of intravital liver bioptates in chronic hepatitis C (CHC). Material and methods. The liver bioptates were obtained by aspiration liver biopsy from 18 patients with CHC. Some visualization methods were used: light and electron microscopy, including examination of semi-thin sections, various methods of fixation and staining. Results. Currently, all types of programmed cell death can be subdivided into external, triggered by signals from the outside of the cell, and internal, caused by disturbances in the functioning of cells. The review provides illustrations and a description of the main types of programmed hepatocyte death in CHC. Morphological signs of internal apoptosis are illustrated by the changes occurring in the mitochondria of hepatocytes (typical and atypical). The participants of the external mechanism of apoptosis associated with the activation of death receptors, are represented by different populations of lymphocytes (cytotoxic, Pit cells). Visualization of lysosomedependent autophagy is represented by illustrations reflecting the main stages and variants of its development (macro-, micro- and chaperone-dependent, mitophagy). Conclusion. Comprehensive morphological diagnostics comprising original methods of fixation and staining of bioptates allows for more accurate visualization of the changes in hepatocytes associated with different variants of programmed cell death and helps to establish the most characteristic pathological and morphological signs for CHC.References
Kanel GC, Korula J. Atlas of Liver Pathology. Amsterdam: Elsevier; 2011. 355 p.
Kuntz E, Kuntz H-D. Hepatology, Principles and Practice: History, Morphology, Biochemistry, Diagnostics, Clinic, Therapy. London: Springer; 2006. 906 p. https://doi.org/10.1007/3-540-28977-1.
Tsyrkunov VM, Andreyev VP, Prokopchik NI. Kravchuk RI. Klinicheskaja morfologija pecheni: nekrozy [Clinical morphology of the liver: necroses]. Zhurnal Grodnenskogo gosudarstvennogo medicinskogo universiteta [Journal of the Grodno State Medical University]. 2017;15(5):557-568. https://doi.org/10.25298/2221-8785-2017-15-5-557-568. (Russian).
Tsyrkunov VM, Andreev VP, Kravchuk RI, Kondratovich IA. Ito stellate cells (hepatic stellate cells) in diagnosis of liver fibrosis. Gastroenterol & Hepatol: Open Access [Internet]. 2019;10(4):213-219. Available from: https://medcraveon-line.com/GHOA/GHOA-10-00384.pdf.
Myadelets OD, Lebedeva EI. Funkcionalnaja morphologija i elementy obshchej patologii pecheni. Vitebsk: VGMU; 2018. 339 p. (Russian).
Tsyrkunov VM, Matsiyeuskaya NV, Lukashyk SP; Tsyrkunov VM, editor. HCV-infekcija. Minsk: Asar; 2012. 480 p. (Russian).
Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972;26(4):239-57. https://doi.org/10.1038/bjc.1972.33.
Kroemer G, El-Deiry WS, Golstein P, Peter ME, Vaux D, Vandenabeele P, Zhivotovsky B, Blagosklonny MV, Malorni W, Knight RA, Piacentini M, Nagata S, Melino G. Classification of cell death: recommendations of the Nomenclature Committee on Cell Death. Cell Death Differ. 2005;12(Suppl 2):1463-7. https://doi.org/10.1038/sj.cdd.4401724.
Malhi H, Guicciardi ME, Gores GJ. Hepatocyte death: a clear and present danger. Physiol Rev. 2010;90(3):1165-94. https://doi.org/10.1152/physrev.00061.2009.
Galluzzi L, Zamzami N, de La Motte Rouge T, Lemaire C, Brenner C, Kroemer G. Methods for the assessment of mitochondrial membrane permeabilization in apoptosis. Apoptosis. 2007;12(5):803-13. https://doi.org/10.1007/s10495-007-0720-1.
Izmenenija plazmaticheskoj membrany vo vremja zaprogrammirovannoj gibeli kletok [Internet]. Available from: https://ru.encyclopediaz.com/plasma-membrane-changes-during-programmed-cell-deaths-655219 (Russian).
Tasdemir E, Galluzzi L, Maiuri MC, Criollo A, Vitale I, Hangen E, Modjtahedi N, Kroemer G. Methods for assessing autophagy and autophagic cell death. Methods Mol Biol. 2008;445:29-76. https://doi.org/10.1007/978-1-59745-157-4_3.
Liu Y, Levine B. Autosis and autophagic cell death: the dark side of autophagy. Cell Death Differ. 2015;22(3):367-76. https://doi.org/10.1038/cdd.2014.143.
Golstein P, Kroemer G. Cell death by necrosis: towards a molecular definition. Trends Biochem Sci. 2007;32(1):37-43. https://doi.org/10.1016/j.tibs.2006.11.001.
Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P, Alnemri ES, Altucci L, Amelio I, Andrews DW, Annicchiarico-Petruzzelli M, Antonov AV, Arama E, Baehrecke EH, Barlev NA, Bazan NG, Bernassola F, Bertrand MJM, Bianchi K, Blagosklonny MV, Blomgren K, Borner C, Boya P, Brenner C, Campanella M, et al. Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ. 2018;25(3):486-541. https://doi.org/10.1038/s41418-017-0012-4.
Andryukov BG, Somova LM, Timchenko NF. Morfologicheskie i molekuljarno-geneticheskie priznaki programmirovannoj kletochnoj gibeli prokariot [Morphological and molecular genetic markers of programmed cell death of prokaryotes]. Zdorovje. Medicinskaja ekologija. Nauka [Health. Medical ecology. Science]. 2015;61(3):4-21. (Russian).
Deev RV, Bilyalov AI, Zhampeisov TM. Modern ideas about cell death. Genes and Cells. 2018;13(1):6-19. https://doi.org/10.23868/201805001.
Mizushima N, Levine B, Cuervo AM, Klionsky DJ. Autophagy fights disease through cellular self-digestion. Nature. 2008;451(7182):1069-75. https://doi.org/10.1038/nature06639.
Dash S, Chava S, Aydin Y, Chandra PK, Ferraris P, Chen W, Balart LA, Wu T, Garry RF. Hepatitis C Virus Infection Induces Autophagy as a Prosurvival Mechanism to Alleviate Hepatic ER-Stress Response. Viruses. 2016;8(5):150. https://doi.org/10.3390/v8050150.
Mizushima N. Autophagy: process and function. Genes Dev. 2007;21(22):2861-73. https://doi.org/10.1101/gad.1599207.
Jin SM, Youle RJ. PINK1- and Parkin-mediated mitophagy at a glance. J Cell Sci. 2012;125(Pt 4):795-9. https://doi.org/10.1242/jcs.093849.
Guicciardi ME, Gores GJ. Life and death by death receptors. FASEB J. 2009;23(6):1625-37. https://doi.org/10.1096/fj.08-111005.
Galluzzi L, Vitale I, Abrams JM, Alnemri ES, Baehrecke EH, Blagosklonny MV, Dawson TM, Dawson VL, El-Deiry WS, Fulda S, Gottlieb E, Green DR, Hengartner MO, Kepp O, Knight RA, Kumar S, Lipton SA, Lu X, Madeo F, Malorni W, Mehlen P, Nuñez G, Peter ME, Piacentini M, Rubinsztein DC, et al. Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012. Cell Death Differ. 2012;19(1):107-20. https://doi.org/10.1038/cdd.2011.96.
Wedemeyer H, He XS, Nascimbeni M, Davis AR, Greenberg HB, Hoofnagle JH, Liang TJ, Alter H, Rehermann B. Impaired effector function of hepatitis C virus-specific CD8+ T cells in chronic hepatitis C virus infection. J Immunol. 2002;169(6):3447-58. https://doi.org/10.4049/jimmunol.169.6.3447.
Tsyrkunov VM, Andreev VP, Prokopchik NI, Kravchuk RI. Klinicheskaja morfologija pecheni: citotoksicheskie limfocity [Clinical liver morphology: cytotoxic lymphocytes]. Zhurnal Grodnenskogo gosudarstvennogo medicinskogo universiteta [Journal of the Grodno State Medical University]. 2018;16(3):337-9. https://doi.org/10.25298/2221-8785-2018-16-3-337-349. (Russian).
Wang H, Tai AW. Mechanisms of Cellular Membrane Reorganization to Support Hepatitis C Virus Replication. Viruses. 2016;8(5):142. https://doi.org/10.3390/v8050142.
Kepp O, Senovilla L, Vitale I, Vacchelli E, Adjemian S, Agostinis P, Apetoh L, Aranda F, Barnaba V, Bloy N, Bracci L, Breckpot K, Brough D, Buqué A, Castro MG, Cirone M, Colombo MI, Cremer I, Demaria S, Dini L, Eliopoulos AG, Faggioni A, Formenti SC, Fučíková J, Gabriele L, et al. Consensus guidelines for the detection of immunogenic cell death. Oncoimmunology. 2014;3(9):e955691. https://doi.org/10.4161/21624011.2014.955691.
Wisse E, Luo D, Vermijlen D, Kanellopoulou C, De Zanger R, Braet F. On the function of pit cells, the liver-specific natural killer cells. Semin Liver Dis. 1997;17(4):265-86. https://doi.org/10.1055/s-2007-1007204.
Bouwens L, Wisse E. Pit cells in the liver. Liver. 1992;12(1):3-9. https://doi.org/10.1111/j.1600-0676.1992.tb00547.x.
Nakatani K, Kaneda K, Seki S, Nakajima Y. Pit cells as liver-associated natural killer cells: morphology and function. Med Electron Microsc. 2004;37(1):29-36. https://doi.org/10.1007/s00795-003-0229-9.
Jakab L. [The liver and the immune system]. Orv Hetil. 2015;156(30):1203-13. https://doi.org/10.1556/650.2015.30190. (Hungarian).
Kuhla A, Eipel C, Abshagen K, Siebert N, Menger MD, Vollmar B. Role of the perforin/granzyme cell death pathway in D-Gal/LPS-induced inflammatory liver injury. Am J Physiol Gastrointest Liver Physiol. 2009;296(5):G1069-76. https://doi.org/10.1152/ajpgi.90689.2008.
Wang F, Gómez-Sintes R, Boya P. Lysosomal membrane permeabilization and cell death. Traffic. 2018;19(12):918-931. https://doi.org/10.1111/tra.12613.
Xie Z, Klionsky DJ. Autophagosome formation: core machinery and adaptations. Nat Cell Biol. 2007;9(10):1102-9. https://doi.org/10.1038/ncb1007-1102.
Ivashkin VT. Mehanizmy immunnoj tolerantnosti i patologii pecheni. Rossijskij zhurnal gastrojenterologii, gepatologii, koloproktologii [Russian Journal of Gastroenterology, Hepatology, Coloproctology]. 2009;19(2):8-13. (Russian).
Crow MT. Hypoxia, BNip3 proteins, and the mitochondrial death pathway in cardiomyocytes. Circ Res. 2002;91(3):183-5. https://doi.org/10.1161/01.res.0000030195.38795.cf.
Moyle G. Mitochondrial toxicity: myths and facts. J HIV Ther. 2004;9(2):45-7.
Vanden Berghe T, Linkermann A, Jouan-Lanhouet S, Walczak H, Vandenabeele P. Regulated necrosis: the expanding network of non-apoptotic cell death pathways. Nat Rev Mol Cell Biol. 2014;15(2):135-47. https://doi.org/10.1038/nrm3737.
Jangamreddy JR, Los MJ. Mitoptosis, a novel mitochondrial death mechanism leading predominantly to activation of autophagy. Hepat Mon. 2012;12(8):e6159. https://doi.org/10.5812/hepatmon.6159.
Izzo V, Bravo-San Pedro JM, Sica V, Kroemer G, Galluzzi L. Mitochondrial Permeability Transition: New Findings and Persisting Uncertainties. Trends Cell Biol. 2016;26(9):655-667. https://doi.org/10.1016/j.tcb.2016.04.006.
Mou Y, Wang J, Wu J, He D, Zhang C, Duan C, Li B. Ferroptosis, a new form of cell death: opportunities and challenges in cancer. J Hematol Oncol. 2019;12(1):34. https://doi.org/10.1186/s13045-019-0720-y.
Galluzzi L, Kroemer G. Necroptosis: a specialized pathway of programmed necrosis. Cell. 2008;135(7):1161-3. https://doi.org/10.1016/j.cell.2008.12.004.
Shi S, Verstegen MMA, Mezzanotte L, de Jonge J, Löwik CWGM, van der Laan LJW. Necroptotic Cell Death in Liver Transplantation and Underlying Diseases: Mechanisms and Clinical Perspective. Liver Transpl. 2019;25(7):1091-1104. https://doi.org/10.1002/lt.25488.
Land WG, Agostinis P, Gasser S, Garg AD, Linkermann A. Transplantation and Damage-Associated Molecular Patterns (DAMPs). Am J Transplant. 2016;16(12):3338-3361. https://doi.org/10.1111/ajt.13963.
Guicciardi ME, Malhi H, Mott JL, Gores GJ. Apoptosis and necrosis in the liver. Compr Physiol. 2013;3(2):977-1010. https://doi.org/10.1002/cphy.c120020.
Land WG, Agostinis P, Gasser S, Garg AD, Linkermann A. DAMP-Induced Allograft and Tumor Rejection: The Circle Is Closing. Am J Transplant. 2016;16(12):3322-3337. https://doi.org/10.1111/ajt.14012.
Afonso MB, Rodrigues PM, Carvalho T, Caridade M, Borralho P, Cortez-Pinto H, Castro RE, Rodrigues CM. Necroptosis is a key pathogenic event in human and experimental murine models of non-alcoholic steatohepatitis. Clin Sci (Lond). 2015;129(8):721-39. https://doi.org/10.1042/CS20140732.
Jorgensen I, Miao EA. Pyroptotic cell death defends against intracellular pathogens. Immunol Rev. 2015;265(1):130-42. https://doi.org/10.1111/imr.12287.
Wang YY, Liu XL, Zhao R. Induction of Pyroptosis and Its Implications in Cancer Management. Front Oncol. 2019;9:971. https://doi.org/10.3389/fonc.2019.00971.
Vitale I, Galluzzi L, Castedo M, Kroemer G. Mitotic catastrophe: a mechanism for avoiding genomic instability. Nat Rev Mol Cell Biol. 2011;12(6):385-92. https://doi.org/10.1038/nrm3115.
Casella G, Munk R, Kim KM, Piao Y, De S, Abdelmohsen K, Gorospe M. Transcriptome signature of cellular senescence. Nucleic Acids Res. 2019;47(14):7294-7305. https://doi.org/10.1093/nar/gkz555.
Kroemer G, Galluzzi L, Vandenabeele P, Abrams J, Alnemri ES, Baehrecke EH, Blagosklonny MV, El-Deiry WS, Golstein P, Green DR, Hengartner M, Knight RA, Kumar S, Lipton SA, Malorni W, Nuñez G, Peter ME, Tschopp J, Yuan J, Piacentini M, Zhivotovsky B, Melino G. Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009. Cell Death Differ. 2009;16(1):3-11. https://doi.org/10.1038/cdd.2008.150.
1.png)
