Cell proliferation and death ofliver mononuclear cells in immunehepatitis induced by concanavalin aand anti-liver antibodies in mice
N.V. Makogon, S.I.Pavlovich, Т.M. Bryzgina,L.I.Alexyuk, V.S. Sukhina, N.G. Grushka, І.M.Аlexeyeva.
O.O.Bogomoletz Institute of Physiology NAS of Ukraine, Kyiv
Abstract
Two types of experimental liver failure in mice were investigated
to study the immune mechanisms of liver disease: 1) T-cell-
mediated injury induced by administration of concanavalin A
(ConA) and 2) antibody-mediated injury induced by administra-
tion of anti-liver antibodies (ALA, ?-globulin fraction of sera
from rabbits immunized with liver tissue). It was established,
that both types of liver injury were accompanied by the activa-
tion of immune processes in the liver, as shown by the increase
of liver mononuclear cell proliferation, estimated using IPO-38
monoclonal antibodies. In contrast to ConA treatment, the im-
mune activation under ALA-treatment was also associated with
the increase in the percentage of plasma cells and small
lymphocytes in liver mononuclear cells. At the same time, an
increase in apoptotic and necrotic mononuclear cell death was
more pronounced under ConA-treatment. This was accompa-
nied by enhanced Fas receptor expression in these cells. Thus,
it was shown that in case of T-cell mediated liver injury, the
balance between cell proliferation and cell death in mononuclear
liver cells was shifted toward the significant increase of apoptotic
and necrotic cell death, particularly Fas-mediated apoptosis,
while immune processes activation and cell proliferation were
more pronounced in the case of antibodies-mediated injury.
References
- Иммунологические методы/Под ред. Г.Фримеля. – М.:Медицина, 1987. – 472 с.
- Камышников В.С. Справочник по клинико-биохи-мическим исследованиям и лабораторной диагностике. –М.: МЕДпресс-информ, 2004. – 912 с.
- Лакин Г.Ф. Биометрия. – М.: Высш. школа, 1980. – 293 с.
- Міхалап С. В. Нові моноклональні антитіла ІПО-38 доядерного антигену, що асоційований з проліферацієюнормальних та злоякіснотрансформованих клітин:Автореф. дис... канд. біол. наук. – К., 1998. – 18 с.
- Труфакин В.А. Иммуноморфологические аспектыаутоиммунных процессов. – Новосибирск: Наука,1983. – 178 с.
- Astaldi G., Verga L. Experimental investigations on theinfluence of x-rays on glycogen content in survivingleucocytes// Experientia. – 1957. – 13, №6. – P.244–245.
- Czaja A.J. Current concepts in autoimmune hepatitis//Ann. Hepatol. – 2005. – 4, №1. – P.6–24.
- Dong Z.J., Wei H.M., Sun R. et al. Isolation of murinehepatic lymphocytes using mechanical dissection for phe-notypic and functional analysis of NK1.1+ cells // WorldJ. Gastroenterol. – 2004. – 10, №13. – P.1928–1933.
- 9. Jones D.E., Palmer J.M., Bennet K. et al. Investigationof a mechanism for accelerated breakdown of immunetolerance to the primary biliary cirrhosis-associatedautoantigen, pyruvate dehydrogenase complex // Lab.Invest. – 2002. – 82, №2. – P.209–211.
- 10. Lapierre P., Djilali-Saiah I., Vitozzi S., Alvarez F. Amurine model of type 2 autoimmune hepatitis: Xenoim-munisation with human antigens // Hepatology. – 2004. –39, №4. – P.1066–1074.
- Lowry O., Boserbrough N.I., Farr A.L., Randal R.I.Protein measurement with the Folin phenol reagent // J.Biol. Chem. – 1951. – 193, №1. – P.265–273.
- Mackay I.R. Hepatoimmunology: a perspective //Immunol. Cell Biol. – 2002. – 80, №1. – P.36–44.
- Mikhalap S.V., Shlapatska L.M., Berdova A.G. et al.Monoclonal antibody IPO-38 in evaluation of prolifera-tive activity of tumor cells // Exp. Oncology. – 2000. –22, №2. – P.36–38.
- Racanelly V., Rehermann B. The liver as an immunolo-gical organ // Hepatology. – 2006. – 43, №2. – P.S54–S62.
- Shimizu S., Eguchi Y., Kamiike W. et al. Involvement ofICE family proteases in apoptosis induced by reoxygen-ation of hypoxic hepatocytes // Amer. J.Phisiol. – 1996. –271, № 6. – P. 949–958.
- Tiegs G., Hentschel J., Wendel A. A T-cell dependentExperimental liver Injury in mice inducible by concana-valin A // J.Clin.Invest. – 1992. – 90, July. – P. 196–203.
- Tiegs G. Cellular and cytokine-mediated mechanisms ofinflammation and its modulation in immune-mediated liverinjury // Z.Gastroenterol. – 2007. – 45, № 1. – P. 63–70.
- Washington M.K. Autoimmune liver disease: overlapand outliers // Modern Pathol. – 2007. – 20, № 6. –P. S15–S30.
- 19. Yamauchi K., Yamaguchi N, Furukawa T. et al. A murinemodel of acute liver injury induced by human monoclonalautoantibody // Hepatology. – 2005. – 42(1), July. – P. 149–155.
- 20. Yoshida Y., Myozaki M., Kuroda E., Yamashita U. Cy-totoxic effect of an anti-liver monoclonal autoantibodyobtained after neonatal thymectomy in mice // J.Autoimmun. – 2001. – 16, №4. – P.373–382.
|