Studies on demyelination in vitro: the requirement of membrane attack components of the complement system

Anti-spinal cord antibodies (anti-SC) cause demyelination of well myelinated mouse cerebellum cultures in the presence of fresh serum. Heating the serum for 30 min at 56 degrees C abolishes the demyelinating activity. We studied the role of complement (c) in demyelination initiated by anti-SC in well myelinated mouse cerebellum cultures. Demyelination was assessed morphologically. The extent of demyelination was correlated to the dose of whole serum C as well as the dose of antibody. To evaluate the requirement of membrane attack components of C, C5b-C9, sister cultures were treated with antibody + C8 deficient human serum (C8D-HS) with and without purified human C8. Extensive demyelination was observed in C8-reconstituted cultures whereas antibody + C8D-HS did not demyelinate, indicating the essential requirement of C5b-8, and/or C5b-9. Extensively demyelinated cultures remyelinated when fresh medium was supplied, suggesting that the process of antibody and C-mediated demyelination is selective for myelin membrane in this system.