Antibody-mediated demyelination in experimental allergic encephalomyelitis is independent of complement membrane attack complex formation.
The effects of decomplementation by cobra venom factor (CVF) on the pathogenesis of inflammation and demyelination in experimental allergic encephalomyelitis (EAE) and acute antibody-mediated demyelinating EAE (ADEAE) have been quantified histologically and immunocytochemically. In rats immunized with 50 micrograms of myelin basic protein in Freund's complete adjuvant containing 100 micrograms heat-killed Mycobacterium tuberculosis H37Ra, clinical signs of EAE were completely suppressed by two injections of CVF given 9 and 12 days post-immunization. Suppression of clinical disease was associated with a dramatic reduction in peri-vascular inflammation in the CNS, although immunohistochemical staining identified small numbers of infiltrating T cells and macrophages. In contrast, CVF treatment had no significant effect on the clinical severity of ADEAE and although C9 deposition within the CNS was virtually abolished, there was no statistically significant decrease in the extent of demyelination or inflammation. These observations indicate that in the absence of complement components C3 and C5 an antibody-dependent cell-mediated cytotoxic response plays an important role in the pathogenesis of antibody-mediated demyelination. The major role of the complement cascade in EAE appears to be the generation of pro-inflammatory factors that enhance the inflammatory response within the CNS in animals facing a mild encephalitogenic challenge.
Piddlesden
S
S
Department of Medicine, University of Wales College of Medicine, Cardiff, Wales, U.K.
Lassmann
H
H
Laffafian
I
I
Morgan
B P
BP
Linington
C
C
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D015938:Complement Membrane Attack Complex / Q000096:biosynthesis*; D003165:Complement System Proteins / Q000378:metabolism; D003711:Demyelinating Diseases / Q000209:etiology*; D004546:Elapid Venoms / Q000494:pharmacology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology*; D006168:Guinea Pigs; D051381:Rats; D011917:Rats, Inbred Lew
D000906:Antibodies; D015938:Complement Membrane Attack Complex; D004546:Elapid Venoms; C016310:cobra venom factor; D003165:Complement System Proteins