Oligodendrocyte cell death in pathogenesis of multiple sclerosis: Protection of oligodendrocytes from apoptosis by complement.
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. It is mediated by activated lymphocytes, macrophages, microglia, and complement. In MS, myelin-forming oligodendrocytes (OLGs) are the targets of inflammatory and immune attacks. OLG death by apoptosis or necrosis causes the cell loss seen in MS plaques. Studies of experimental allergic encephalomyelitis (EAE) in caspase 11-deficient mice show that caspase-mediated death of OLGs is critical to demyelination. Complement activation may affect MS pathogenesis through activated terminal complex C5b-9, which promotes demyelination, and through sublytic C5b-9, which protects OLGs from apoptosis. By inducing EAE in C5-deficient mice, we showed that complement C5 promotes axon preservation and new myelin formation, which protect OLGs from apoptosis. These findings indicate that activated complement C5b-9 plays a proinflammatory role in acute MS but may also protect OLGs from death in chronic MS.
Cudrici
Cornelia
C
Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Niculescu
Teodora
T
Niculescu
Florin
F
Shin
Moon L
ML
Rus
Horea
H
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D020169:Caspases / Q000172:deficiency; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D003167:Complement Activation / Q000187:drug effects*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D053222:Fas Ligand Protein / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051379:Mice; D009103:Multiple Sclerosis / Q000503:physiopathology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009836:Oligodendroglia / Q000166:cytology* / Q000187:drug effects; D012307:Risk Factors; D012680:Sensitivity and Specificity
D053222:Fas Ligand Protein; D018696:Neuroprotective Agents; D020169:Caspases