Research Interests
My laboratory is interested to understand the pathophysiology of complement system in relation to the brain glial cells. The complement system and activation of the terminal pathway appears to play a major role in inflammatory response in the brain. The terminal pathway leads to assembly of the terminal complement complexes C5b-7, C5b-8 and C5b-9. C5b-7 is cytolytically inactive and does not form pores while C5b-9 induces cell lysis. In sublytic attack, cells survive by eliminating short-lived channels through endocytosis and exocytosis. For instance activation of complement and assembly sublytic C5b-9 induces not only down-regulation of specific myelin gene expression but also facilitate activation of cell cycle in oligodendrocyte (OLG). In order to clarify the role of C5b-9 in cell cycle activation we used differential display and cloned a new gene R esponse G ene to C omplement (RGC)-32. RGC-32 is localized on chromosome 13 and is induced by C5b-9 and growth factors. RGC-32 binds to cdc2/cyclin B1 complex, increased the cdc2 kinase activity and its overexpression induces cell cycle activation. Our data suggest that RGC-32 function as a regulator of cell cycle activation through activation of cdc2 kinase. Interestingly activation of cell cycle is associated with increased survival and protection of OLG from apoptosis through inhibition of mitochondrial pathways. Thus, it appears that complement activation and C5b-9 assembly play a protective role in vitro. Recently this protective role was also investigated in vivo using a C5 deficient mice and an experimental autoimmune encephalomyelitis (EAE) model. Our results indicate that the absence of C5 resulted in fiber loss and extensive scarring, whereas presence of C5-favored axonal survival and more efficient remyelination. These data suggest that complement C5, which is essential for the formation of C5b-9, is necessary for the efficient recovery in EAE by promoting remyelination, facilitating axonal survival and preventing extensive scaring.
