MULTIPLE-SCLEROSIS - OLIGODENDROCYTES DISPLAY CELL DEATH-RELATED MOLECULES IN-SITU BUT DO NOT UNDERGO APOPTOSIS

To investigate whether apoptosis is involved in the fare of oligodendr ocytes in chronic multiple sclerosis lesions, the pro-apoptotic molecu les fas and tumor necrosis factor receptors and the anti-apoptotic mol ecule bcl-2 were examined by immunohistochemistry, and DNA fragmentati on was assessed by an end labeling technique. Fas and both tumor necro sis factor receptors were preferentially expressed on oligodendrocytes in multiple sclerosis lesions, this phenotype being more evident at t he lesion edge, The ligand for fast, was constitutively present at hig h levels on microglia. The anti-apoptotic molecule bcl-2 was selective ly expressed on oligodendrocytes in silent lesions and on astrocytes i n active lesions. These molecules were also detected in control materi al, albeit at lower levels, In chronic active lesions, a few inflammat ory cells displayed fas reactivity, whereas the majority expressed bcl -2, DNA fragmentation was found in a number of infiltrating cells and some microglia, whereas, with one possible exception, oligodendrocytes showed no evidence of apoptosis. Thus, while apoptosis is involved in the elimination of infiltrating cells, it plays little or no role in oligodendrocyte depletion in multiple sclerosis, a process that may be related to a lyric pathway. In addition, microglia constitutively dis played the ligand for fas, and appeared to be the major effector cell population in the central nervous system.