Immunohistochemical Localization of BcI-2 in the Spinal Cords of Rats with Experimental Autoimmune Encephalomyelitis

Moon, Chang-Jong;Lee, Yong-Duk;Shin, Tae-Kyun

  • Published : 20020000

Abstract

We examined the localization of the anti-apoptotic molecule BcI-2 in the spinal cords of Lewis rats with experimental autoimmune encephalomyelitis (EAE). Western blot analysis showed that BcI-2 was constitutively expressed in normal spinal cords, and weakly increased in response to complete Freund's adjuvant(CFA) immunization. In EAE, with infiltration of inflammatory cells into spinal cords, BcI-2 declined during the peak stage and further decreased during the recovery stage. Immunohistochemically, some neurons and glial cells constitutively expressed BcI-2 in normal rat spinal cords. In the spinal cords of rats with EAE, BcI-2 was also immunoreacted in some perivascular inflammatory cells while some brain cells, such as neurons and GFAP (+) astrocytes showed less BcI-2 immunoreaction. These findings suggest that in EAE, BcI-2 expression in the CNS host cells decreases with CNS inflammation, possibly progressing to cell death in some cases, while the survival of host cells, including neurons, astrocytes, and some inflammatory cells, is associated with activation of the anti-apoptotic molecule BcI-2. Taking all into considerations, its is postulated that BcI-2 either beneficially or detrimentally functions in some host cells depending on the activation stage of each cell type.

Keywords

References

  1. Bauer, J., Bradl, M., Hickley, W.F., Forss-Petter, S., Breitschopf, H., Linington, C., Wekerle, H., Lassmann, H. T-cell apoptosis in inflammatory brain lesions: destruction of T cells does not depend on antigen recognition. Am. J. Pathol. 1998, 153, 715-724.
  2. Bonetti, B., Pohl, J., Gao, Y.L., Raine, C.S. Cell death during autoimmune demyelination: effector but not target cells are eliminated by apoptosis. J. Immunol. 1997, 159, 5733-5741.
  3. Bonetti, B., Raine, C.S. Multiple sclerosis: oligodendrocytes display cell death related molecules in situ but do not undergo apoptosis. Ann. Neural. 1997,42, 74-84.
  4. Brune, B., Gotz, C., Messmer, U.K., Sandau, K., Hirvonen, M.R., Lapetina, E.G. Superoxide formation and macrophage resistance to nitric oxide-mediated apoptosis. J. BioI. Chem. 1997, 272, 7253-7258.
  5. Kohji, T., Tanuma, N., Aikawa, Y., Kawazoe, Y., Suzuki, Y., Kohyama, K., Matsumoto, Y. Interaction between apoptotic cells and reactive brain cells in the central nervous system of rats with autoimmune encephalomyelitis. J. Neuroimmunol. 1998, 82, 168-74.
  6. Korner, H., Sedgwick, J.D. Tumour necrosis factor and lymphotoxin: molecular aspects and role in tissuespecific autoimmunity. Immunol. Cell. BioI. 1996, 74(5), 465-472.
  7. Melkova. Z., Lee, S.B., Rodriguez, D., Esteban, M. Bcl-2 prevents nitric oxide-mediated apoptosis and poly(ADP-ribose) polymerase cleavage. F.E.B.S. Lett. 1997, 403, 273-278.
  8. Moon, C., Kim, S., Wie, M., Kim, H., Cheong, J., Park, J., Jee, Y., Tanuma, N., Matsumoto, Y., Shin, T. Increased expression of p53 and Bax in the spinal cords of rats with experimental autoimmune encephalomyelitis. Neurosci. Lett. 2000, 289(1), 41-44.
  9. Offen, D., Kaye, J.F., Bernard, O., Merims, D., Coire, C.I., Panet, H., Melamed, E., Ben-Nun, A. Mice overexpressing Bcl-2 in their neurons are resistant to myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE). J. Mol. Neurosci. 2000, 15(3), 167-176.
  10. Ohmori, K., Hong, Y., Fujiwara, M., Matsumoto, Y. In situ demonstration of proliferating cells in the rat central nervous system during experimental autoimmune encephalomyelitis. Evidence suggesting that most infiltrating T cells do not proliferate in the target organ. Lab. Invest. 1992, 66, 54-62.
  11. Okuda, Y., Sakoda, S., Fujimura, H., Yanagihara, T. Nitric oxide via an inducible isoform of nitric oxide synthase is a possible factor to eliminate inflammatory cells from the central nervous system of mice with experirrental allergic encephalomyelitis. J. Neuroimmunol. 1997, 73, 107-116.
  12. Raine, C.S., Cannella, B., Duijvestijn, A.M., Cross, AR Homing to central nervous system vasculature by antigen-specific lymphocytes. Il. Lymphocyte/endothelial cell adhesion during the initial stages of autoimmune demyelination. Lab. Invest. 1990, 63, 476-489.
  13. Raine, C.S., Cannella, B., Duijvestijn, A.M., Cross, AR Homing to central nervous system vasculature by antigen-specific lymphocytes. Il. Lymphocyte/endothelial cell adhesion during the initial stages of autoimmune demyelination. Lab. Invest. 1990, 63, 476-489.
  14. Reed, J.C., Jurgensmeier, J.M., Matsuyama, S. Bcl-2 family proteins and mitochondria. Biochem. Biophys. Acta. 1998, 1366, 127-137.
  15. Schmied, M, Breitschopf, H., Gold, R., Zischler, H., Rothe, G., Wekerle, H., Lassmann, H. Apoptosis of T lymphocytes in experimental autoimmune encephalomyelitis. Evidence for programmed cell death as a mechanism to control inflammation in the brain. Am. J. Pathol. 1993, 143, 446-452.
  16. Shin, T., Kojirna, T., Tanuma, N., Ishihara, Y., Matsumoto, Y. The subarachnoid space as a site for precursor T cell proliferation and effector T cell selection in experimental autoimmune encephalomyelitis. J. Neuroimmunol. 1995, 56, 171-178.
  17. Waggoner, S.E., Baunooh, D.A., Anderson, S.A., leigh, F., Zegaja, V.G. Bcl-2 protein expression associated with resistance to apoptosis in clear cell adenocarcinoma of the vagina and cervix expressing wild-type p53. Ann. Surg. Oncol. 1998, 5, 544-547.
  18. White, C.A., McCombe, P.A., Pender, M.P. The roles of Fas, Fas ligand and BcI-2 in T cell apoptosis in the central nervous system in experimental autoimmune encephalomyelitis. J. Neuroimmunol. 1998, 82, 47-55. https://doi.org/10.1016/S0165-5728(97)00187-2
  19. Zettl, U.K., Kuhlmann, T., Bruck, W. Bcl-2 expressing T lymphocytes in multiple sclerosis lesions. Neuropathol. Appl. Neurobiol. 1998, 24, 202-208.
  20. Zirbes, T.K., Lorenzen, J., Baldus, S.E., Moenig, S.P., Wolters, U., Ottlik, A., Thiele, J., Holscher, A.H., Dienes, H.P. Apoptosis and expression of BcI-2 are inverse factors influencing tumor cell turnover in primary carcinoid tumors of the lung. Histopathology 1998, 33, 123-128.