Annals of the Russian academy of medical sciencesAnnals of the Russian academy of medical sciencesВестник Российской академии медицинских наук0869-60472414-3545"Paediatrician" Publishers LLC30410.15690/vramn.v67i5.274PHYSIOLOGY: CURRENT ISSUESАКТУАЛЬНЫЕ ВОПРОСЫ ФИЗИОЛОГИИMECHANISMS OF PROTECTIVE INFLUENCE OF ENDOTOXIN-ACTIVATED KUPFFER CELLS ON HEPATOCYTESМЕХАНИЗМЫ ПРОТЕКТОРНОГО ДЕЙСТВИЯ АКТИВИРОВАННЫХ ЭНДОТОКСИНОМ КЛЕТОК КУПФЕРА НА ГЕПАТОЦИТЫElbakidzeG. M.ЭлбакидзеГ. М.
Russian Federation

доктор биологических наук, академик РАЕН, директор Медико-биологического центра Ассоциации содействия международному центру научной культуры — Всемирная лаборатория Адрес: 125057, Москва, Ленинградский пр-т, д. 71 Тел.: (967) 130-96-01

gmelbakidze@hotmail.comAssociation for World Laboratory, Biomedical CenterМедико-биологический центр Ассоциации содействия международному центру научной культуры — Всемирная лаборатория, Москва23052012675Вестник Российской академии медицинских наук485407082015Copyright ©; 2012, "Paediatrician" Publishers LLCCopyright ©; 2012, Издательство "Педиатръ"2012"Paediatrician" Publishers LLCИздательство "Педиатръ"https://vestnikramn.spr-journal.ru/jour/about/submissionshttps://vestnikramn.spr-journal.ru/jour/article/view/304

Various aspects of protective and damaging influences of endotoxin-activated Kupffer cells on hepatocytes are discussed. Requests for protective subcellular mechanism activated by Kupffer cells mediators were formulated. Two possible mechanisms of activated Kupffer cells protective influence on hepatocytes which satisfy these requests are considered. One of them may operate via hepatocyte non-specific reaction to damage initiated by Kupffer cells mediators. Another one may work through activation of endotoxin-dependent tissue stress mechanism in hepatocytes. The data confirm the development of non-specific reaction to damage and the mechanism of tissue stress realized by means of tissue-specific effector in hepatocytes under endotoxin-activated Kupffer cells influence.

В статье обсуждаются различные аспекты протекторного и повреждающего действия активированных эндотоксином клеток Купфера на гепатоциты. Сформулированы требования, которым должен удовлетворять активируемый медиаторами клеток Купфера внутриклеточный протекторный механизм у гепатоцитов. Рассмотрены два возможных механизма протекторного действия активированных клеток Купфера на гепатоциты, удовлетворяющие этим требованиям. Один из них реализуется на основе активируемой медиаторами клеток Купфера неспецифической реакции гепатоцитов на повреждение, другой — путем активации в гепатоцитах механизма тканевого стресса. Представлены данные, свидетельствующие о формировании в гепатоцитах под действием активированных эндотоксином клеток Купфера неспецифической реакции на повреждение, а также механизма тканевого стресса, реализуемого при участии тканеспецифического эффектора.

Kupffer cellshepatocytesendotoxintissue stressadaptationклетки Купферагепатоцитыэндотоксинтканевый стрессадаптация1. Kmiec Z. Cooperation of liver cells in health and disease. Adv. Anat. Embryol. Cell Biol. 2001; 161: III–XIII.2. Bellezzo J.M., Britton R.S., Bacon B.R., Fox E.S. LPS-mediated NF-kappa beta activation in rat Kupffer cells can be induced independently of CD14. Am. J. Physiol. 1996; 270 (6 Pt. 1): 956–961.3. Yao H.-W., Li J., Chen J.-Q., Xu S.-Y. Leflunomide attenuates hepatocyte injury by inhibiting Kupffer cells. World J. Gastroenterol. 2004; 10 (11): 1608–1611.4. Meltzer M.S. Macrophage activation for tumor cytotoxicity: characterization of priming and trigger signals during lymphokine activation. J. Immunol. 1981; 127 (1): 179–183.5. Johnson W.J., Marino P.A., Schreiber R.D., Adams D.O. Sequential activation of murine mononuclear phagocytes for tumor cytolysis: differential expression of markers by acrophages in the several stages of development. J. Immunol. 1983; 131 (2): 1038–1043.6. Hoek J. B., Pastorino J.G. Ethanol, oxidative stress, and cytokineinduced liver cell injury. Alcohol. 2002; 27 (1): 63–68.7. Roberts R.A., Ganey P. E., Ju C., Kamendulis, L. M. et al. Role of the Kupffer cell in mediating hepatic toxicity and carcinogenesis. Toxicol. Sci. 2007; 96 (1): 2–15.8. Kresse M., Latta M., Kunstle G. et al. Kupffer cell-expressed membrane-bound TNF mediates melphalan hepatotoxicity via activation of both TNF receptors. J. Immunol. 2005; 175 (6): 4076–4083.9. He Q., Kim J., Sharma R. P. Fumonisin B1 hepatotoxicity in mice is attenuated by depletion of Kupffer cells by gadolinium chloride. Toxicology. 2005; 207 (1): 137.10. Andres D., Sanchez-Reus I., Bautista M. et al. Depletion of Kupffer cell function by gadolinium chloride attenuates thioacetamideinduced hepatotoxicity. Expression of metallothionein and HSP70. Biochem. Pharmacol. 2003; 66 (6): 917–926.11. Tejima K., Arai M., Ikeda H. et al. Ischemic preconditioning protects hepatocytes via reactive oxygen species derived from Kupffer cells in rats. Gastroenterology. 2004; 127 (5):1488–1496.12. Tapia G., Santibanez C., Farias J. Kupffer-cell activity is essential for thyroid hormone rat liver preconditioning. Mol. Cell Endocrinol. 2010; 323 (2): 292–297.13. Prins H.A., Holtz R., Boelens P.G., Diks J. et al. The role of Kupffer cells after major liver surgery. Clin. Nutr. 2003; 22 (1): 53.14. Prins H. A., Meijer C., Boelens P. G., Diks, J. et al. Kupffer celldepleted rats have a diminished acute-phase response following major liver resection. Shock (Augusta, Ga.). 2004; 21 (6): 561–565.15. Han D., Ybanez M.D., Ahmadi S., Yeh K. Redox regulation of tumor necrosis factor signaling. Antioxid. Redox. Signal. 2009; 11 (9): 2245–2263.16. Ju C., Reilly T. P., Bourdi M. et al. Protective role of Kupffer cells in acetaminophen-induced hepatic injury in mice. Chem. Res. Toxicol. 2002; 15 (12): 1504–1513.17. Winwood P.J., Arthur M.J. Kupffer cells: their activation and role in animal models of liver injury and human liver disease. Seminars in Liver Disease. 1993; 13 (1): 50–59.18. Alexanderov V.Ia. Reaqtivnost` cletoq i belqi. L.: Nauca. 1985. 318.19. E`i`dus L.KH. Nespetcifichesqaia reaqtciia cletoq i radiochuvstvitel`nost`. M.: Atomizdat. 1977. 156.20. Kalendo G.S. O vozmozhnosti adaptatcionnogo sindroma — stressa na cletochnom urovne i ego roli v reaqtcii cletqi na obluchenie. Usp. sovr. biol. 1972; 73 (1): 59–80.21. Elbakidze G.M., Elbakidze A.G. Principles of Tissue Growth Intratissue Regulation. Collierville: Inst.Publ. 2009. 163.22. E`lbaqidze G.M., E`lbaqidze A.G. Mehanizmy` gipermetabolichesqikh sostoianii`. Vestnic RAMN. 2011; 7: 50–54.23. Brown A.D., Mozhenoq T.P. Nespetcifichesqii` adaptatcionny`i` sindrom cletochnoi` sistemy`. L.: Nauca. 1987. 230.24. Kaina B. Cross-resistance studies with V79 Chinese hamster cells adapted to the mutagenic or clastogenic effect of N-methyl-N’- nitro-N-nitrosoguanidine. Mutat. Res. 1983; 111: 341–352.25. Vijayalaxmi L., Burkart W. Resistance and cross-resistance to chromosome damage in human blood lymphocytes adapted to bleomycin. Mutat. Res. 1989; 211: 1–5.26. Vijayalaxmi L, Leal B.Z., Deahl T.S. and Meltz M.L. Variability in adaptive response to low dose radiation in human blood lymphocytes: consistent results from chromosome aberrations and micronuclei. Mutat. Res. 1995; 348: 45–50.27. New K.J., Eaton S., Elliott K.R.F., Spitz L. et al. Effect of lipopolysaccharide and cytokines on oxidative metabolism in neonatal rat hepatocytes. J. Pediatr. Surg. 2001; 36: 338–340.28. Rivera C.A., Bradford B.U., Seabra V., Thurman R.G. Role of endotoxin in the hypermetabolic state after acute ethanol exposure. Am. J. Physiol. 1998; 275 (6 Pt. 1): 1252–1258.29. Schemmer P., Enomoto N., Bradford B.U., Bunzendahl H. et al. Activated Kupffer cells cause a hypermetabolic state after gentle in situ manipulation of liver in rats. Am. J. Physiol. Gastrointestinal. 2001; 280. (6): 1076–1082.30. Smith R.A., Baglioni C., The active form of TNF is a trimer. J.Biol. Chem. 1987; 262: .6951–6954.31. Yokoyama Y., Nimura Y., Nagino M., Bland K.I., Chaudry I.H. Role of thromboxane in producing hepatic injury during hepatic stress. Arch. Surg. 2005; 140 (8): 801–807.32. E`lbaqidze G.M., Chelidze M.A., E`lbaqidze I.M. Tqanespetcifichesqaia reguliatciia transporta ionov qal`tciia termostabil`ny`m qomutonom iz pecheni qry`sy`. Doclady` AN. 1990; 313 (2): 474–478.33. E`lbaqidze G.M., E`lbaqidze A.G. Kuliqova L.A. Issledovanie uchastiia cletoq Coopfera v initciatcii protcessa prodigiozanzavisimogo naqopleniia qomutona v pecheni qry`sy`. Docl. AN. 2006; 407 (1): 119–123.34. E`lbaqidze G.M., E`lbaqidze A.G., Medentcev G.A. Issledovanie vliianiia prodigiozan-zavisimogo qomutona na medlenny`i` vy`hod ionov qal`tciia iz matriqsa mitohondrii` razlichnoi` tqanevoi` i vidovoi` prinadlezhnosti. Docl. AN. 2011; 437 (6): v pechati.35. E`lbaqidze G.M., Foi`gel` A.G., Maevsqii` E.I., Bohua B.T. i dr. Issledovanie tqanespetcifichesqoi` Sa2+-zavisimoi` reguliatcii mitohondrial`ny`kh protcessov termostabil`ny`m qomutonom iz pecheni qry`sy`. Docl. AN. 1992; 324 (1): 214–219.36. Elbakidze G.M., Elbakidze A.G. Tissue stress — the tissuespecific intratissue adaptation mechanism. VIII World Congr. of Int. Soc. for Adapt. Med., Abstract book. Moscow. 2006. 135–136.37. Elbakidze G.M. Comuton — the effector of liver tissue stress. Canad. J. Physiol. Pharmacol. 1994; 72 (1): 610–612.38. E`lbaqidze G.M., Medentcev A.G. Issledovanie uslovii` aqqumuliatcii in vitro termostabil`nogo qomutona iz pecheni qry`sy`. Docl. AN. 2002; 387 (4): 553–556.39. E`lbaqidze G.M., Medentcev A.G., E`lbaqidze A.G., Shary`shev A.A. Issledovanie vnutricletochnoi` organizatcii qomutonnoi` reguliatcii mitohondrial`ny`kh protcessov v pecheni qry`sy`. Docl. AN. 2006; 408 (5): 704–707.40. Morgunov I.G., E`lbaqidze G.M., Medentcev A.G. Vy`delenie i ochistqa qomuton-produtciruiushchego fermenta iz pecheni qry`sy`. Docl. AN. 2003; 389 (2): 67–70.41. E`lbaqidze G.M., Chelidze M.A., E`lbaqidze I.M., Foi`gel` A.G. i dr. Ingibitorny`i` analiz tqanespetcifichesqogo dei`stviia vy`soqoochishchennogo termostabil`nogo qomutona iz pecheni qry`sy` na dy`hanie mitohondrii`. Docl. AN SSSR. 1991; 320 (1): 227–231.42. E`lbaqidze G.M., Chelidze M.A., Medentcev A.G., Bohua B.T. i dr. Generirovanie gidropereqisi v protcesse fermentativnogo oqisleniia termostabil`nogo qomutona iz pecheni qry`sy`. Docl. AN. 1994; 336 (1): 120–123.43. Brovqo F.A., E`lbaqidze G.M., Bohua B.T. Fraqtcionirovanie qomutondioqsigenazy` iz pecheni qry`sy`. Docl. AN. 1994; 338 (3): 401–403.44. Elbakidze G.M., Chelidze M.A., Bokhua B.T. Enzymatic oxidation of the thermostable comuton from rat liver in liver mitochondria. 22-nd FEBS Meeting, Abstract book, Stockholm. 1993. 185.44. Tcitologiia fermentov / Pod red. D.B. Rudina. M.: Mir. 1971. 397.45. Wisse E., Knook D. The investigation of sinusoidal cells: a new approach to the study of liver function. Progress in liver deseases / H. Popper (ed.). N.-Y.: Raven Press. 1979: 151–176.46. E`lbaqidze G.M., E`lbaqidze I.M. Aqtivatciia vnutritqanevogo qontrolia e`nergetichesqogo metabolizma v pecheni pri povy`shenii nagruzqi na spetcial`ny`e funqtcii i ee povrezhdenie gepatotoqsinom.. Docl. AN SSSR. 1986; 291 (3): 719–723.47. E`lbaqidze G.M., Chelidze M.A., E`lbaqidze I.M. Vliianie odnoqratnogo vvedeniia fenobarbitala i chety`rekhkhloristogo ugleroda na aqtivnost` qomutona v pecheni qry`sy`. Izv. AN SSSR. Ser. biol. 1989; 5: 666–673.48. Saris N.-E.L., Carafoli E. A historical review of cellular calcium handling, with emphasis on mitochondria. Biochem. (Moscow). 2005; 70 (2): 187–194.49. Bernardi P., Azzone G.F. A membrane potential-modulated pathway for Ca2+ efflux in rat liver mitochondria. FEBS Lett. 1982: 139: 13–16.50. Bernardi P., Scorrano L., Colonna R., Petronilli V. et al. Mitochondria and cell death. Mechanistic aspects and methodological issues. Eur. J. Biochem. 1999; 264 (3): 687–701