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Immunpathologie der Multiplen Sklerose

  • T. Kuhlmann
  • W. Brück
Conference paper
  • 71 Downloads

Zusammenfassung

Die Multiple Sklerose (MS) ist die häufigste entzündliche demyelinisierende Erkrankung des zentralen Nervensystems (ZNS). Der entmarkte Plaque ist das Hauptcharakteristikum dieser Erkrankung. Die demyelinisierten Herde sind bevorzugt im Bereich der Kleinhirnstiele, der Nervi optici, der periventrikulären weißen Substanz und im Rückenmark lokalisiert, seltener finden sie sich in den Kerngebieten des Hirnstamms oder in der Großhirnrinde.Innerhalb der Plaques kommt es zu einer Zerstörung des Myelins und/oder der Oligodendrozyten, begleitet von einer Entzündungsreaktion (Lassmann 1998; Prineas 1985). Das entzündliche Infiltrat setzt sich hauptsächlich aus Lymphozyten und Makrophagen zusammen. Trotz dieser grundsätzlichen Gemeinsamkeiten gibt es jedoch Kriterien, anhand derer unterschiedlichehistologische Subtypen definiert werden können (Lucchinetti et al. 1996). In MS-Läsionen finden sich ganz unterschiedliche Veränderungen hinsichtlich der Myelin- und Oligodendrozytenschädigung. Einige Patienten weisen einen fast vollständigen Verlust an Oligodendrozyten in den Plaques auf, bei anderen ist lediglich das Myelin zerstört. Gelegentlich kommt es auch zu einer Rekrutierung von Oligodendrozytenvorläuferzellen (Lucchinetti et al. 1999). Mit einem einheitlichen Schädigungsmechanismus lassen sich diese unterschiedlichen histopathologischen Befunde nur schwer erklären. Vielmehr ist anzunehmen, dass verschiedene immunologische und toxische Mechanismen für diese unterschiedlichen histologischen Muster verantwortlich sind.

References

  1. Adelmann M, Wood J, Benzei I, Fiori P, Lassmann H, Matthieu J-M, Gardinier MJ, Dornmair K, Linington C (1995) The N-terminal domain of the myelin oligodendrocyte glycoprotein (MOG) induces acute demyelinating experimental autoimmune encephalomyelitis in the Lewis rat. J Neuroimmunol 63:17–27PubMedCrossRefGoogle Scholar
  2. Amor S, Groome N, Linington C, Morris MM, Dornmair K, Gardinier MV, Matthieu J-M, Baker D (1994) Identification of epitopes of myelin oligodendrocyte glycoprotein for the induction of experimental allergic encephalomyelitis in SJL and Biozzi AB/H mice. J Immunol 153:4349–4356PubMedGoogle Scholar
  3. Barac-Latas V, Suchanek G, Breitschopf H, Stuehler A, Wege H, Lassmann H (1997) Patterns of oligodendrocyte pathology in coronavirus-induced subacute demyelinating encephalomyelitis in the Lewis rat. Glia 19:1–12PubMedCrossRefGoogle Scholar
  4. Berger T, Weerth S, Kojima K, Linington C, Wekerle H, Lassmann H (1997) Experimental autoimmune encephalomyelitis: the antigen specificity of T lymphocytes determines the topography of lesions in the central and peripheral nervous system. Lab Invest 76:355–364PubMedGoogle Scholar
  5. Bitsch A, Kuhlmann T, da Costa C, Bunkowski S, Polak T, Brück W (2000) Tumour necrosis factor alpha mRNA expression in early multiple sclerosis lesions: correlation with demyelinating activity and oligodendrocyte pathology. Glia 29:366–375PubMedCrossRefGoogle Scholar
  6. Burgmaier G, Schönrock ML, Kuhlmann T, Richter-Landsberg C, Brück W (2000) Association of increased bcl-2 expression with rescue from TNF-a induced cell death in the oligodendrocyte cell line OLN-93. J Neurochem (in press)Google Scholar
  7. Cammer W (2000) Effects of TNFa on immature and mature oligodendrocytes and their progenitors in vitro. Brain Res 864:213–219PubMedCrossRefGoogle Scholar
  8. D’Souza SD, Alinauskas KA, Antel JP (1996) Ciliary neurotrophic factor selectively protects human oligodendrocytes from tumor necrosis factor-mediated injury. J Neurosci Res 43:289–298PubMedCrossRefGoogle Scholar
  9. Griot-Wenk M, Griot C, Pfister H, Vandevelde M (1991) Antibody-dependent cellular cytotoxicity in antimyelin antibody-induced oligodendrocyte damage in vitro. J Neuroimmunol 33:145–155PubMedCrossRefGoogle Scholar
  10. Griot C, Vandevelde M, Richard A, Peterhans E, Stocker R (1990) Selective degeneration of oligodendrocytes mediated by reactive oxygen species. Free Rad Res Commun 11:181–193CrossRefGoogle Scholar
  11. Itoyama Y, Sternberger NH, Webster HD (1980) Immunocytochemical observations on the distribution of myelin associated glycoprotein and myelin basic protein in multiple sclerosis lesions. Ann Neurol 7:167–177PubMedCrossRefGoogle Scholar
  12. Itoyama Y, Webster HD, Sternberger NH, Richardson EP, Walker DL, Quarles RH, Padgett BL (1982) Distribution of papovavirus, myelin-associated glycoprotein, and myelin-basic protein in progressive multifocal leukencephalopathy lesions. Ann Neurol 11:396–407PubMedCrossRefGoogle Scholar
  13. Johns TG, de Rosbo NK, Menon KK, Abo S, Gonzales MF, Bernard CCA (1995) Myelin oligodendrocyte glycoprotein induces a demyelinating encephalomyelitis resembling multiple sclerosis. J Immunol 154:5536–5541PubMedGoogle Scholar
  14. Juurlink BJH, Thorburne SK, Hertz L (1998) Peroxide-scavenging deficit underlies oligodendrocyte susceptibility to oxidative stress. Glia 22:371–378PubMedCrossRefGoogle Scholar
  15. Lassmann H (1998) Pathology of multiple sclerosis. In: Compston A, Ebers G, Lassmann Het al. (eds) McAlpine’s Multiple Sclerosis. Churchill Livingstone, London, pp 323–358Google Scholar
  16. Linington C, Engelhardt B, Kapocs G, Lassmann H (1992) Induction of persistently demyelinated lesions in the rat following the repeated adoptive transfer of encephalitogenic T cells and demyelinating antibody. J Neuroimmunol 40:219–224PubMedCrossRefGoogle Scholar
  17. Lucchinetti C, Brück W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H (1999) A quantitative analysis of oligodendrocytes in multiple sclerosis lesions. A study of 113 cases. Brain 122:2279–2295PubMedCrossRefGoogle Scholar
  18. Lucchinetti C, Brück W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H (2000) Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 47:707–717PubMedCrossRefGoogle Scholar
  19. Lucchinetti CF, Brück W, Rodriguez M, Lassmann H (1996) Distinct patterns of Multiple Sclerosis pathology indicates heterogeneity in pathogenesis. Brain Pathol 6:259–274PubMedCrossRefGoogle Scholar
  20. Ludwin SK, Johnson ES (1981) Evidence for a “Dying-back” gliopathy in demyelinating disease. Ann Neurol 9:301–305PubMedCrossRefGoogle Scholar
  21. Merrill JE, Ignarro LJ, Sherman MP, Melinek J, Lane TE (1993) Microglial cell cytotoxicity of oligodendrocytes is mediated through nitric oxide. J Immunol 151:2132–2141PubMedGoogle Scholar
  22. Mitrovic B, Ignarro LJ, Montestruque S, Smoll A, Merrill JE (1994) Nitric oxide as a potential pathological mechanism in demyelination: its differential effects on primary glial cells in vitro. Neuroscience 61:575–585PubMedCrossRefGoogle Scholar
  23. Piddlesden S, Lassmann H, Laffafian I, Morgan BP, Linington C (1991) Antibody-mediated demyelination in experimental allergic encephalomyelitis is independent of complement membrane attack complex formation. Clin Exp Immunol 83:245–250PubMedCrossRefGoogle Scholar
  24. Prineas JW (1985) The neuropathology of multiple sclerosis. In: Koetsier JC (ed) Demyelinating diseases. Elsevier Science Publishers, Amsterdam, pp 213–257Google Scholar
  25. Probert L, Akassoglou K, Pasparakis M, Kontogeorgos G, Kollias G (1995) Spontaneous inflammatory demyelinating disease in transgenic mice showing central nervous system- specific expression of tumor necrosis factor a. Proc Natl Acad Sci USA 92:11294–11298PubMedCrossRefGoogle Scholar
  26. Rodriguez M, Scheithauer B (1994) Ultrastructure of multiple sclerosis. Ultrastruct Pathol 18:3–13PubMedCrossRefGoogle Scholar
  27. Rodriguez M, Scheithauer BW, Forbes G, Kelly PJ (1993) Oligodendrocyte injury is an early event in lesions of multiple sclerosis. Mayo Clin Proc 68:627–636PubMedGoogle Scholar
  28. Scolding NJ, Jones J, Compston DAS, Morgan BP (1990) Oligodendrocyte susceptibility to injury by T-cell perforin. Immunology 70:6–10PubMedGoogle Scholar
  29. Selmaj K, Raine CS, Farooq M, Norton WT, Brosnan CF (1991a) Cytokine cytotoxicity against oligodendrocytes. Apoptosis induced by lymphotoxin. J Immunol 147:1522–1529Google Scholar
  30. Selmaj K, Raine CS, Cannella B, Brosnan CF (1991b) Identification of lymphotoxin and tumor necrosis factor in multiple sclerosis lesions. J Clin Invest 87:949–954PubMedCrossRefGoogle Scholar
  31. Selmaj KW, Raine CS (1988) Tumor necrosis factor mediates myelin and oligodendrocyte damage in vitro. Ann Neurol 23:339–346PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2001

Authors and Affiliations

  • T. Kuhlmann
  • W. Brück

There are no affiliations available

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