vtioВестник трансплантологии и искусственных органовRussian Journal of Transplantology and Artificial Organs1995-1191Academician V.I.Shumakov National Medical Research Center of Transplantology and Artificial Organs", Ministry of Health of the Russian Federation10.15825/1995-1191-2011-3-73-81vtio-419Research ArticleОбзор литературыLiterature ReviewsВОЗМОЖНАЯ РОЛЬ ПРОТЕАСОМ ПЕЧЕНИ В РЕАЛИЗАЦИИ МЕХАНИЗМОВ ТРАНСПЛАНТАЦИОННОЙ ТОЛЕРАНТНОСТИPOSSIBLE ROLE OF LIVER PROTEASOMES IN THE REALIZATION OF MECHANISMS OF TRANSPLANTATION TOLERANCEБожокГ. А.BozhokG. A.bozhokgaru@mail.ruКарповаЯ. Д.KarpovaYa. D.ЛюпинаЮ. В.LyupinaYu. V.ЛегачЕ. И.LegachE. I.БогомягковаЮ. В.BogomyagkovaYu. V.БондаренкоТ. П.BondarenkoT. P.ШароваН. П.SharovaN. P.Институт проблем криобиологии и криомедицины НАН Украины, ХарьковРоссияInstitute for Problems of Cryobiology and Cryomedicine of National Academy of Science of Ukraine, KharkovRussian FederationИнститут биологии развития им. Н.К. Кольцова РАН, МоскваРоссияN.K. Koltzov Institute of Developmental Biology of Russian Academy of Sciences, MoscowRussian Federation201120062014133ВЕСТНИК ТРАНСПЛАНТОЛОГИИ И ИСКУССТВЕННЫХ ОРГАНОВ том XIII No 3–20117381Copyright © Божок Г.А., Карпова Я.Д., Люпина Ю.В., Легач Е.И., Богомягкова Ю.В., Бондаренко Т.П., Шарова Н.П., 20112011Божок Г.А., Карпова Я.Д., Люпина Ю.В., Легач Е.И., Богомягкова Ю.В., Бондаренко Т.П., Шарова Н.П.Bozhok G.A., Karpova Y.D., Lyupina Y.V., Legach E.I., Bogomyagkova Y.V., Bondarenko T.P., Sharova N.P.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.transpl.ru/vtio/article/view/419

В отличие от большинства органов в печени неспецифический иммунитет преобладает над адаптивным, а в ответ на презентацию антигена предпочтительнее развивается не защитная иммунная реакция, а им- мунологическая толерантность. Считается, что толерантность обеспечивают ряд процессов, таких, как апоптоз реактивных Т-клеток, уклонение их от иммунного ответа и активная супрессия иммунных ре- акций. В то же время есть основания полагать, что важную роль в регуляции иммунного ответа печени играют протеасомы, внутриклеточные мультипротеазные белковые комплексы. Об этом свидетельствует факт применения протеасомного ингибитора бортезомиба в трансплантологии в качестве иммуносупрес- санта. Иммунные 26S- и 20S-протеасомы участвуют в образовании антигенных олигопептидов и выпол- няют ключевую роль в Т-клеточном иммунном ответе. Было показано, что пул протеасом подвергается существенным изменениям в процессе онтогенеза иммуно-компетентных органов. Знание особенностей функционирования протеасом и закономерностей изменения соотношения их форм позволит выявить механизмы, отвечающие за направленность вектора иммунного ответа на отторжение или принятие трансплантата. 

In contrast to the majority of organs in liver non-specific immunity predominates over adaptive one, and in response to the antigen presentation develops preferably not immune reaction but immunological tolerance. Tolerance is considered to provide some processes, such as apoptosis of reactive T-cells, immune deviation and active suppression of immune reactions. At the same time there are the grounds for believing that an important role in regulation of liver immune response is played by proteasomes, intracellular multiprotease protein complexes. This is confirmed by the fact of application of proteasome inhibitor bortezomib as immune suppressor in transplantology. Immune 26S- and 20S-proteoasomes participate in the formation of antigen oligopeptides and play a key role in T-cell immune response. It has been shown that the pool of proteasomes is subjected to significant changes during ontogenesis of immune competent organs. The changes in the pool of proteasosmes occur likely during the development of specific tolerance in transplantation too. The knowledge of the peculiarities of proteasome functioning and regularities of alterations of their shapes will enable the revealing of the mechanisms responsible for either graft rejection or acceptance. 

донор-специфическая толерантностьтрансплантацияиммунология печениконститутивные и иммунные протеасомыdonor-specific tolerancetransplantationliver immunologyconstitutive and immune proteasomesReferencesБожок Г.А., Кирошка В.В., Тищенко Ю.О., Легач Е.И. Предтрансплантационное введение донорских лим- фоцитов пролонгирует выживаемость аллогенной ткани яичников у овариэктомированных животных реципиентов // Проблеми ендокринної патології. 2009. No4. С. 15–18.Божок Г.А., Кирошка В.В., Тищенко Ю.О., Легач Е.И. Предтрансплантационное введение донорских лим- фоцитов пролонгирует выживаемость аллогенной ткани яичников у овариэктомированных животных реципиентов // Проблеми ендокринної патології. 2009. No4. С. 15–18.Ройт А., Бростофф Д., Мейл Д. Иммунология. М.: Мир, 2000. 592 с.Ройт А., Бростофф Д., Мейл Д. Иммунология. М.: Мир, 2000. 592 с.Шумаков В.И. Трансплантология: Руководство для врачей. М.: Медицина, 1995. 575 с.Шумаков В.И. Трансплантология: Руководство для врачей. М.: Медицина, 1995. 575 с.Arrigo A.P., Tanaka K., Goldberg A.L., Welch W.J. Iden- tity of the 19S ‘prosome’ particle with the large multi- functional protease complex of mammalian cells (the proteasome) // Nature. 1988. Vol. 331. P. 192–194.Arrigo A.P., Tanaka K., Goldberg A.L., Welch W.J. Iden- tity of the 19S ‘prosome’ particle with the large multi- functional protease complex of mammalian cells (the proteasome) // Nature. 1988. Vol. 331. P. 192–194.Barbatis C., Woods J., Morton J.A., Fleming K.A. et al. Immunohistochemical analysis of HLA (A, B, C) anti- gens in liver disease using a monoclonal antibody // Gut. 1981. Vol. 22 (12). P. 985–991.Barbatis C., Woods J., Morton J.A., Fleming K.A. et al. Immunohistochemical analysis of HLA (A, B, C) anti- gens in liver disease using a monoclonal antibody // Gut. 1981. Vol. 22 (12). P. 985–991.Bertolino P., Bowen D.G., McCaughan G.W., Fazekas de St Groth B. Antigen-specific primary activation of CD8+ T cells within the liver // J. Immunol. 2001. Vol. 166 (9). P. 5430–5438.Bertolino P., Bowen D.G., McCaughan G.W., Fazekas de St Groth B. Antigen-specific primary activation of CD8+ T cells within the liver // J. Immunol. 2001. Vol. 166 (9). P. 5430–5438.Calne R.Y. Mechanisms in the acceptance of organ grafts // Br. Med. Bull. 1976. Vol. 32. P. 107–112.Calne R.Y. Mechanisms in the acceptance of organ grafts // Br. Med. Bull. 1976. Vol. 32. P. 107–112.Calne R.Y., Sells R.A., Pena J.R., Davis D.R. et al. In- duction of immunological tolerance by porcine liver al- lografts // Nature. 1969. Vol. 223. P. 472–476.Calne R.Y., Sells R.A., Pena J.R., Davis D.R. et al. In- duction of immunological tolerance by porcine liver al- lografts // Nature. 1969. Vol. 223. P. 472–476.Cascio P., Hilton C., Kisselev A.F., Rock K.L. et al. 26S proteasomes and immunoproteasomes produce mainly N-extended versions of an antigenic peptide // EMBO J. 2001. Vol. 20 (10). P. 2357–2366.Cascio P., Hilton C., Kisselev A.F., Rock K.L. et al. 26S proteasomes and immunoproteasomes produce mainly N-extended versions of an antigenic peptide // EMBO J. 2001. Vol. 20 (10). P. 2357–2366.Chalermskulrat W., McKinnon K.P., Brickey W.J., Neu- ringer I.P. et al. Combined donor specific transfusion and anti-CD154 therapy achieves airway allograft tole- rance // Thorax. 2006. Vol. 61 (1). P. 61–67.Chalermskulrat W., McKinnon K.P., Brickey W.J., Neu- ringer I.P. et al. Combined donor specific transfusion and anti-CD154 therapy achieves airway allograft tole- rance // Thorax. 2006. Vol. 61 (1). P. 61–67.Chen C.H., Kuo L.M., Chang Y., Wu W. et al. In vivo immune modulatory activity of hepatic stellate cells in mice // Hepatology. 2006. Vol. 44. P. 1171–1181.Chen C.H., Kuo L.M., Chang Y., Wu W. et al. In vivo immune modulatory activity of hepatic stellate cells in mice // Hepatology. 2006. Vol. 44. P. 1171–1181.Chen M., Tabaczewski P., Truscott S.M., Van Kaer L. et al. Hepatocytes express abundant surface class I MHC and efficiently use transporter associated with antigen processing, tapasin, and low molecular weight poly- peptide proteasome subunit components of antigen pro- cessing and presentation pathway // J. Immunol. 2005. Vol. 175 (2). P. 1047–1055.Chen M., Tabaczewski P., Truscott S.M., Van Kaer L. et al. Hepatocytes express abundant surface class I MHC and efficiently use transporter associated with antigen processing, tapasin, and low molecular weight poly- peptide proteasome subunit components of antigen pro- cessing and presentation pathway // J. Immunol. 2005. Vol. 175 (2). P. 1047–1055.Coux O., Tanaka K., Goldberg A.L. Structure and func- tions of the 20S and 26S proteasomes // Annu. Rev. Bio- chem. 1996. Vol. 65. P. 801–847.Coux O., Tanaka K., Goldberg A.L. Structure and func- tions of the 20S and 26S proteasomes // Annu. Rev. Bio- chem. 1996. Vol. 65. P. 801–847.Crispe I.N., Matthew G., Ingo K., Beena J. et al. Cellular and molecular mechanisms of liver tolerance // Immuno- logical Reviews. 2006. Vol. 213. P. 101–118.Crispe I.N., Matthew G., Ingo K., Beena J. et al. Cellular and molecular mechanisms of liver tolerance // Immuno- logical Reviews. 2006. Vol. 213. P. 101–118.Dhanireddy K.K., Bruno D.A., Weaver T.A., Xu H. et al. Portal venous donor-specific transfusion in conjunction with sirolimus prolongs renal allograft survival in non- human primates // Am. J. Transplant. 2009. Vol. 9 (1). P. 124–131.Dhanireddy K.K., Bruno D.A., Weaver T.A., Xu H. et al. Portal venous donor-specific transfusion in conjunction with sirolimus prolongs renal allograft survival in non- human primates // Am. J. Transplant. 2009. Vol. 9 (1). P. 124–131.ErhardtA.,BiburgerM.,PapadopoulosT.,TiegsG.IL-10, regulatory T cells, and Kupffer cells mediate tolerance in concanavalin A-induced liver injury in mice // Hepatolo- gy. 2007. Vol. 45. P. 475–485.ErhardtA.,BiburgerM.,PapadopoulosT.,TiegsG.IL-10, regulatory T cells, and Kupffer cells mediate tolerance in concanavalin A-induced liver injury in mice // Hepatolo- gy. 2007. Vol. 45. P. 475–485.Griffin T.A., Nandi D., Cruz M., Fehling H.J. et al. Im- munoproteasome assembly: cooperative incorporation of interferon gamma (IFN-gamma)-inducible subunits // J. Exp. Med. 1998. Vol. 187. P. 97–104.Griffin T.A., Nandi D., Cruz M., Fehling H.J. et al. Im- munoproteasome assembly: cooperative incorporation of interferon gamma (IFN-gamma)-inducible subunits // J. Exp. Med. 1998. Vol. 187. P. 97–104.Guillaume B., Chapiro J., Stroobant V., Colau D. et al. Two abundant proteasome subtypes that uniquely pro- cess some antigens presented by HLA class I molecu- les // Proc. Natl. Acad. Sci. USA. 2010. Vol. 107 (43). P. 18599–18604.Guillaume B., Chapiro J., Stroobant V., Colau D. et al. Two abundant proteasome subtypes that uniquely pro- cess some antigens presented by HLA class I molecu- les // Proc. Natl. Acad. Sci. USA. 2010. Vol. 107 (43). P. 18599–18604.Iwata H., Umeda Y., Matsuno Y., Yoshikawa S. et al. Pro- longation of xenograft survival by combining donor-spe- cific intravenous presensitization with FK 506 // Trans- plant. Proc. 2002. Vol. 34. P. 2745–2748.Iwata H., Umeda Y., Matsuno Y., Yoshikawa S. et al. Pro- longation of xenograft survival by combining donor-spe- cific intravenous presensitization with FK 506 // Trans- plant. Proc. 2002. Vol. 34. P. 2745–2748.Jung T., Bader N., Grune T. Oxidized proteins: intracel- lular distribution and recognition by the proteasome // Arch. Biochem. Biophys. 2007. Vol. 462 (2). P. 231–237.Jung T., Bader N., Grune T. Oxidized proteins: intracel- lular distribution and recognition by the proteasome // Arch. Biochem. Biophys. 2007. Vol. 462 (2). P. 231–237.Kamada N., Davies H.F.S., Roser B. Reversal of trans- plantation immunity by liver grafting // Nature. 1981. Vol. 292. P. 840–842.Kamada N., Davies H.F.S., Roser B. Reversal of trans- plantation immunity by liver grafting // Nature. 1981. Vol. 292. P. 840–842.Kenick S., Lowry R.P., Forbes R.D.S., Lisbona R. Pro- longed cardiac allograft survival following portal venous inoculation of allogeneic cells: What is «hepatic toleran- ce?»// Transplant. Proc. 1987. Vol. 19. P. 478–479.Kenick S., Lowry R.P., Forbes R.D.S., Lisbona R. Pro- longed cardiac allograft survival following portal venous inoculation of allogeneic cells: What is «hepatic toleran- ce?»// Transplant. Proc. 1987. Vol. 19. P. 478–479.Kloetzel P.M., Ossendorp F. Proteasome and peptidase function in MHC-class-I-mediated antigen presentati- on // Curr. Opin. Immunol. 2004. Vol. 16 (1). P. 76–81.Kloetzel P.M., Ossendorp F. Proteasome and peptidase function in MHC-class-I-mediated antigen presentati- on // Curr. Opin. Immunol. 2004. Vol. 16 (1). P. 76–81.Knolle P.A., Gerken G. Local control of the immune response in the liver // Immunological Reviews. 2000. Vol. 174. P. 21–34.Knolle P.A., Gerken G. Local control of the immune response in the liver // Immunological Reviews. 2000. Vol. 174. P. 21–34.Knolle P.A., Germann T., Treichel U., Uhrig A. et al. En- dotoxin downregulates T cell activation by antigen-pre- senting liver sinusoidal endothelial cells // J. Immunol. 1999. Vol. 162. P. 1401–1407.Knolle P.A., Germann T., Treichel U., Uhrig A. et al. En- dotoxin downregulates T cell activation by antigen-pre- senting liver sinusoidal endothelial cells // J. Immunol. 1999. Vol. 162. P. 1401–1407.Markees T.G., Phillips N.E., Noelle R.J., Shultz L.D. et al. Prolonged survival of mouse skin allografts in re- cipients treated with donor splenocytes and antibody to CD40 ligand // Transplantation. 1997. Vol. 64 (2). P. 329– 335.Markees T.G., Phillips N.E., Noelle R.J., Shultz L.D. et al. Prolonged survival of mouse skin allografts in re- cipients treated with donor splenocytes and antibody to CD40 ligand // Transplantation. 1997. Vol. 64 (2). P. 329– 335.29. 30. 31.29. 30. 31.33.33.35.35.39. 40.39. 40.Oko A., Idasiak-Piechocka I., Pawlaczyk K., Wruk M. et al. Prolongation of rat kidney graft survival after ino- culation of allogeneic spleen cells: the effect of various routes of cell transfer // Ann. Transplant. 2002. Vol. 7 (2). P. 51–53.Oko A., Idasiak-Piechocka I., Pawlaczyk K., Wruk M. et al. Prolongation of rat kidney graft survival after ino- culation of allogeneic spleen cells: the effect of various routes of cell transfer // Ann. Transplant. 2002. Vol. 7 (2). P. 51–53.Onoe T., Ohdan H., Tokita D., Shishida M. et al. Liver sinusoidal endothelial cells tolerize T cells across MHC barriers in mice // J. Immunol. 2005. Vol. 175. P. 139– 146.Onoe T., Ohdan H., Tokita D., Shishida M. et al. Liver sinusoidal endothelial cells tolerize T cells across MHC barriers in mice // J. Immunol. 2005. Vol. 175. P. 139– 146.Opelz G., Wujciak T., Dohler B., Scherer S. et al. HLA compatibility and organ transplant survival. Collaborati- ve Transplant Study // Rev. Immunogenet. 1999. Vol. 1. P. 334–342.Opelz G., Wujciak T., Dohler B., Scherer S. et al. HLA compatibility and organ transplant survival. Collaborati- ve Transplant Study // Rev. Immunogenet. 1999. Vol. 1. P. 334–342.Patel R.D., Vanikar A.V., Aziz F.A., Shah P.R. et al. Ah- medabad tolerance induction protocol and chronic renal allograft dysfunction: pathologic observations and clini- cal implications // Diagn. Pathol. 2009. Vol. 4. P. 4–9. Parker D.C., Greiner D.L., Phillips N.E., Appel M.C. et al. Survival of mouse pancreatic islet allografts in re- cipients treated with allogeneic small lymphocytes and antibody to CD40 ligand // Proc. Natl. Acad. Sci. USA. 1995. Vol. 92 (21). 9560–9564.Patel R.D., Vanikar A.V., Aziz F.A., Shah P.R. et al. Ah- medabad tolerance induction protocol and chronic renal allograft dysfunction: pathologic observations and clini- cal implications // Diagn. Pathol. 2009. Vol. 4. P. 4–9. Parker D.C., Greiner D.L., Phillips N.E., Appel M.C. et al. Survival of mouse pancreatic islet allografts in re- cipients treated with allogeneic small lymphocytes and antibody to CD40 ligand // Proc. Natl. Acad. Sci. USA. 1995. Vol. 92 (21). 9560–9564.Parker G.A., Picut C.A. Liver immunobiology //Toxicol. Pathol. 2005. Vol. 33 (1). P. 52–62.Parker G.A., Picut C.A. Liver immunobiology //Toxicol. Pathol. 2005. Vol. 33 (1). P. 52–62.Rock K.L., Goldberg A.L. Degradation of cell proteins and the generation of MHC class I-presented peptides // Annu. Rev. Immunol. 1999. Vol. 17. P. 739–779.Rock K.L., Goldberg A.L. Degradation of cell proteins and the generation of MHC class I-presented peptides // Annu. Rev. Immunol. 1999. Vol. 17. P. 739–779.Sato Y., Farges O., Buffello D., Hatakeyama K. et al.Sato Y., Farges O., Buffello D., Hatakeyama K. et al.Impact of 70% partial hepatectomy on administration of donor leukocytes in cardiac transplantation in rats // Transplant. Proc. 1998. Vol. 30. P. 3873–3875.Impact of 70% partial hepatectomy on administration of donor leukocytes in cardiac transplantation in rats // Transplant. Proc. 1998. Vol. 30. P. 3873–3875.Sato Y., Ichida T., Watanabe H., Yamamoto S. et al. Re- peating intraportal donor-specific transfusion may indu- ce tolerance following adult living-related donor liver transplantation // Hepatogastroenterology. 2003. Vol. 50 (51). P. 601–606.Sato Y., Ichida T., Watanabe H., Yamamoto S. et al. Re- peating intraportal donor-specific transfusion may indu- ce tolerance following adult living-related donor liver transplantation // Hepatogastroenterology. 2003. Vol. 50 (51). P. 601–606.Sharova N.P., Zakharova L.A., Astakhova T.M., Karpo- va Ya.D. et al. New approach to study of T cellular im- munity development: Parallel investigation of lymphoid organ formation and changes in immune proteasome amount in rat early ontogenesis // Cell. Immunol. 2009. Vol. 256. P. 47–55.Sharova N.P., Zakharova L.A., Astakhova T.M., Karpo- va Ya.D. et al. New approach to study of T cellular im- munity development: Parallel investigation of lymphoid organ formation and changes in immune proteasome amount in rat early ontogenesis // Cell. Immunol. 2009. Vol. 256. P. 47–55.Sheng Sun D., Iwagaki H., Ozaki M., Ogino T. et al. Pro- longed survival of donor-specific rat intestinal allograft by administration of bone-marrow-derived immature dendritic cells // Transpl. Immunol. 2005. Vol. 14 (1). P. 17–20.Sheng Sun D., Iwagaki H., Ozaki M., Ogino T. et al. Pro- longed survival of donor-specific rat intestinal allograft by administration of bone-marrow-derived immature dendritic cells // Transpl. Immunol. 2005. Vol. 14 (1). P. 17–20.Tewari M.K., Sinnathamby G., Rajagopal D., Eisen- lohr L.C. A cytosolic pathway for MHC class II-restric- ted antigen processing that is proteasome and TAP de- pendent // Nat. Immunol. 2005. Vol. 6. P. 287–294. Tokita D., Shishida M., Ohdan H., Onoe T. et al. Liver sinusoidal endothelial cells that endocytose allogeneic cells suppress T cells with indirect allospecificity // J. Immunol. 2006. Vol. 177. P. 3615–3624.Tewari M.K., Sinnathamby G., Rajagopal D., Eisen- lohr L.C. A cytosolic pathway for MHC class II-restric- ted antigen processing that is proteasome and TAP de- pendent // Nat. Immunol. 2005. Vol. 6. P. 287–294. Tokita D., Shishida M., Ohdan H., Onoe T. et al. Liver sinusoidal endothelial cells that endocytose allogeneic cells suppress T cells with indirect allospecificity // J. Immunol. 2006. Vol. 177. P. 3615–3624.Tung T.H., Doolabh V.B., Mackinnon S.B., Mohanaku- mar T. et al. Survival of long nerve allografts following donor antigen pretreatment: a pilot study // J. Reconstr. Microsurg. 2006. Vol. 22 (6). P. 443–449.Tung T.H., Doolabh V.B., Mackinnon S.B., Mohanaku- mar T. et al. Survival of long nerve allografts following donor antigen pretreatment: a pilot study // J. Reconstr. Microsurg. 2006. Vol. 22 (6). P. 443–449.Visekruna A., Joeris T., Schmidt N., Lawrenz M. et al. Comparative expression analysis and characterization of 20S proteasomes in human intestinal tissues: The prote- asome pattern as diagnostic tool for IBD patients // In- flamm. Bowel Dis. 2009. Vol. 15 (4). P. 526–533.Visekruna A., Joeris T., Schmidt N., Lawrenz M. et al. Comparative expression analysis and characterization of 20S proteasomes in human intestinal tissues: The prote- asome pattern as diagnostic tool for IBD patients // In- flamm. Bowel Dis. 2009. Vol. 15 (4). P. 526–533.Voges D., Zwickl P., Baumeister W. The 26S proteaso- me: a molecular machine designed for controlled pro- teolysis // Annu. Rev. Biochem. 1999. Vol. 68. P. 1015– 1068.Voges D., Zwickl P., Baumeister W. The 26S proteaso- me: a molecular machine designed for controlled pro- teolysis // Annu. Rev. Biochem. 1999. Vol. 68. P. 1015– 1068.Walsh R.C., Everly J.J., Brailey P., Rike A.H. et al. Prote- asome inhibitor-based primary therapy for antibody-me- diated renal allograft rejection // Transplantation. 2010. Vol. 89 (3). P. 277–284.Walsh R.C., Everly J.J., Brailey P., Rike A.H. et al. Prote- asome inhibitor-based primary therapy for antibody-me- diated renal allograft rejection // Transplantation. 2010. Vol. 89 (3). P. 277–284.Walz J., Erdmann A., Kania M., Typke D. et al. 26S prote- asome structure revealed by three-dimensional electron microscopy // J. Struct. Biol. 1998. Vol. 121. P. 19–29.Walz J., Erdmann A., Kania M., Typke D. et al. 26S prote- asome structure revealed by three-dimensional electron microscopy // J. Struct. Biol. 1998. Vol. 121. P. 19–29.Watanabe T., Kudo M., Chiba T., Wakatsuki Y. Molecular mechanisms of portal vein tolerance // Hepatology Re- search. 2008. Vol. 38. P. 441–449.Watanabe T., Kudo M., Chiba T., Wakatsuki Y. Molecular mechanisms of portal vein tolerance // Hepatology Re- search. 2008. Vol. 38. P. 441–449.Wilk S., Orlowski M. Evidence that pituitary cation-sen- sitive neutral endopeptidase is a multicatalytic protease complex // J. Neurochem. 1983. Vol. 40 (3). P. 842–849.Wilk S., Orlowski M. Evidence that pituitary cation-sen- sitive neutral endopeptidase is a multicatalytic protease complex // J. Neurochem. 1983. Vol. 40 (3). P. 842–849.Yang L., Du Temple B., Khan Q., Zhang L. Mechanisms of long-term donor-specific allograft survival induced by pretransplant infusion of lymphocytes // Blood. 1998. Vol. 91 (1). P. 324–330.Yang L., Du Temple B., Khan Q., Zhang L. Mechanisms of long-term donor-specific allograft survival induced by pretransplant infusion of lymphocytes // Blood. 1998. Vol. 91 (1). P. 324–330.

The authors declare that there are no conflicts of interest present.