C5b-9 complement complex in autoimmune demyelination and multiple sclerosis: dual role in neuroinflammation and neuroprotection.
Complement system activation plays an important role in innate and acquired immunity. Activation of complement leads to the formation of C5b-9 terminal complex. While C5b-9 can promote cell lysis, sublytic assembly of C5b-9 on plasma membranes induces cell cycle activation and survival. Multiple sclerosis (MS) and its animal model experimental allergic encephalomyelitis (EAE) are inflammatory demyelinating diseases of the central nervous system (CNS) mediated by activated lymphocytes, macrophages/microglia and the complement system. Complement activation may contribute to the pathogenesis of these diseases through its dual role: the ability of activated terminal complex C5b-9 to promote demyelination and the capacity of sublytic C5b-9 to protect oligodendrocytes (OLG) from apoptosis. By inducing EAE in C5-deficient mice, we showed that complement C5 promotes remyelination and protects oligodendrocytes from apoptotic cell death. These findings indicate that activation of complement C5b-9 plays a pro-inflammatory role in the acute phase of the disease, but may also be neuroprotective during the chronic phase of the disease.
Rus
Horea
H
University of Maryland at Baltimore, School of Medicine, Department of Neurology, 655 W. Baltimore Street, BRB 12-016, Baltimore, MD 21201, USA. hrus@umaryland.edu
Cudrici
Cornelia
C
Niculescu
Florin
F
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D003167:Complement Activation / Q000276:immunology; D015938:Complement Membrane Attack Complex / Q000172:deficiency / Q000276:immunology*; D020278:Demyelinating Autoimmune Diseases, CNS / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D006801:Humans; D051379:Mice; D009103:Multiple Sclerosis / Q000276:immunology*; D009413:Nerve Fibers, Myelinated / Q000276:immunology*; D018696:Neuroprotective Agents / Q000276:immunology*; D009836:Oligodendroglia / Q000276:immunology
D015938:Complement Membrane Attack Complex; D018696:Neuroprotective Agents