The role of complement in the pathogenesis of experimental allergic encephalomyelitis.
The role of complement in the pathogenesis of demyelination and inflammation has been investigated in a synergistic model of acute experimental allergic encephalomyelitis (EAE) in the Lewis rat. Depletion of serum complement with cobra venom factor (CVF) suppressed the clinical expression of acute inflammatory EAE induced either by immunization with 50 micrograms guinea pig basic protein (MBP) in Freund's complete adjuvant, or by the passive transfer of 10(7), but not 5 X 10(7) MBP activated spleen cells. Despite the suppression of clinical disease in actively induced EAE, treatment with CFF only had a significant effect on the severity of CNS inflammation in early disease (12 days postimmunization) when the number of inflammatory foci was reduced by 35%. Three days later this difference had resolved and no significant difference could be detected in the severity of CNS inflammation, although control animals exhibited severe disease, the CVF treated group being clinically normal. Demyelination in these models is initiated by systemic injection of the antimyelin oligodendrocyte glycoprotein (MOG) monoclonal antibody, 8-18C5, which in vitro lyses oligodendrocytes in a dose, Fc and complement-dependent manner and in vivo induces extensive CNS demyelination in rats with EAE. Treatment with CVF reduced the ability of this antibody to initiate demyelination in vivo and furthermore, its F(ab)2' fragment had no effect on the clinical course of EAE and was unable to initiate demyelination in normal animals. Complement-dependent mechanisms are therefore involved both in the clinical expression of acute inflammatory lesions and in the pathogenesis of antibody-mediated demyelination in EAE.
Linington
C
C
Department of Medicine, University of Wales College of Medicine, Cardiff, UK.
Morgan
B P
BP
Scolding
N J
NJ
Wilkins
P
P
Piddlesden
S
S
Compston
D A
DA
D000818:Animals; D000911:Antibodies, Monoclonal; D002470:Cell Survival; D003169:Complement Inactivator Proteins / Q000494:pharmacology; D003165:Complement System Proteins / Q000276:immunology*; D004546:Elapid Venoms / Q000494:pharmacology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D007114:Immunization; D007116:Immunization, Passive; D004676:Myelin Basic Protein / Q000276:immunology; D009186:Myelin Sheath / Q000276:immunology; D009836:Oligodendroglia / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew
D000911:Antibodies, Monoclonal; D003169:Complement Inactivator Proteins; D004546:Elapid Venoms; D004676:Myelin Basic Protein; C016310:cobra venom factor; D003165:Complement System Proteins