PMID: 11340645May 8, 2001Paper

Structural dynamics of oligodendrocyte lysis by perforin in culture: relevance to multiple sclerosis

Journal of Neuroscience Research
R ZeineC S Raine

Abstract

The mechanism by which oligodendrocytes are depleted from active lesions in multiple sclerosis (MS) is not clear but many reports implicate a cytolytic process. The most applied animal model for MS, chronic relapsing experimental autoimmune encephalomyelitis (EAE), has been established in inbred strains of mice, especially SJL and PL. Studies on oligodendrocytes from these strains in vitro have been hampered to date by an inability to grow these cells from mouse CNS tissue. We report here a successful method to culture SJL mouse oligodendrocytes and have analyzed lysis of these cells in vitro mediated by the pore-forming protein, perforin, a candidate effector molecule in inflammatory demyelination. Cultures were exposed to murine perforin, 36-72 hemolytic U, for up to 2.5 hr and examined using the oligodendrocyte phenotypic markers O4, galactocerebroside and myelin basic protein (MBP), in addition to a membrane dye (DiI) and a marker of necrosis, propidium iodide, (PI). Cultures were imaged chronologically by phase contrast, immunofluorescence, digital, light and electron microscopy. Findings showed that the majority of oligodendrocytes were killed within 60-90 min via pore expansion and ultimately, membrane disruption. The st...Continue Reading

References

Oct 1, 1979·Acta Neuropathologica·J Kirk
Jun 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·D M OjciusJ D Young
Aug 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·K SelmajC S Raine
May 28, 1990·Brain Research·T C RuijsJ P Antel
Apr 1, 1988·Annals of Neurology·K W Selmaj, C S Raine
Dec 1, 1965·Brain : a Journal of Neurology·O Périer, A Grégoire
Aug 1, 1995·Immunological Reviews·C C LiuJ D Young
Apr 1, 1995·Immunology Today·C C LiuJ D Young
Jan 1, 1994·Ultrastructural Pathology·M Rodriguez, B Scheithauer
Jul 1, 1993·Mayo Clinic Proceedings·M RodriguezP J Kelly
Jul 1, 1996·Brain Pathology·C F Brosnan, C S Raine
Nov 28, 1996·The New England Journal of Medicine·C C LiuJ D Young
Dec 1, 1996·The Journal of Experimental Medicine·S D D'SouzaJ P Antel
Feb 1, 1997·Journal of Neuropathology and Experimental Neurology·S K Ludwin
Dec 31, 1997·The Journal of Experimental Medicine·B ZhangT Tabira
May 29, 1998·European Journal of Immunology·Y MatsumotoN Tanuma
Nov 7, 1999·Journal of Autoimmunity·S Pouly, J P Antel
Dec 3, 1999·Brain : a Journal of Neurology·C LucchinettiH Lassmann
Jan 13, 2000·Neuropathology and Applied Neurobiology·J E Merrill, N J Scolding
Feb 7, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·S A FraserD Hudig

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Citations

May 3, 2003·Molecular and Cellular Neurosciences·Una F FitzGeraldSusan C Barnett
Sep 13, 2011·Protein Expression and Purification·Peter James BakerJin Kim Montclare
Mar 2, 2010·Expert Review of Neurotherapeutics·Jens WatzlawikMoses Rodriguez

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