Related Experiment Videos
Attenuation of experimental autoimmune demyelination in complement-deficient mice
S Nataf1, S L Carroll, R A Wetsel
1Departments of Microbiology, Pathology, and Medicine, University of Alabama, Birmingham, AL 35294, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|November 9, 2000
Summary
Complement activation contributes to central nervous system (CNS) inflammation and myelin damage in experimental allergic encephalomyelitis (EAE). Complement deficiency significantly reduces EAE severity and protects against demyelination.
Area of Science:
- Neuroimmunology
- Complement system biology
- Demyelinating diseases
Background:
- The precise mechanisms driving CNS inflammation and myelin destruction in multiple sclerosis (MS) and its animal model, experimental allergic encephalomyelitis (EAE), are not fully understood.
- Complement activation is hypothesized to be crucial in MS and EAE, mediating inflammatory cell recruitment, enhancing myelin phagocytosis, and causing direct oligodendrocyte damage via the membrane attack complex.
- Evaluating the in vivo role of complement in autoimmune demyelination has been challenging due to the absence of suitable, non-toxic inhibitors.
Purpose of the Study:
- To elucidate the role of the complement system in an antibody-independent EAE model.
- To investigate the necessity of complement component 3 (C3) and factor B in the pathogenesis of EAE and CNS demyelination.
Main Methods:
- Utilized mice genetically deficient in either C3 or factor B to study an Ab-independent EAE model.
- Assessed disease severity, inflammatory cell infiltration (macrophages, T cells), and demyelination in the CNS of complement-deficient and wild-type mice following EAE induction.
Main Results:
- Complement-deficient mice (C3(-/-) and factor B(-/-)) exhibited markedly reduced EAE disease severity compared to wild-type littermates.
- While meningeal and perivascular inflammation occurred in all groups, C3(-/-) and factor B(-/-) mice showed significantly less parenchymal infiltration by macrophages and T cells.
- CNS tissues from EAE-induced C3(-/-) and factor B(-/-) mice were protected from demyelination relative to wild-type controls.
Conclusions:
- The complement system, specifically C3 and factor B, plays a critical role in mediating CNS inflammation and demyelination in this model of EAE.
- Complement activation is essential for efficient inflammatory cell infiltration into the CNS parenchyma and subsequent myelin destruction.
- These findings suggest that targeting the complement system could be a viable therapeutic strategy for inflammatory demyelinating diseases like MS.