Role of the C5b-9 complement complex in cell cycle and apoptosis

Assembly of C5b-9 on cell membranes results in transmembrane channels and c auses cell death. When the number of C5b-9 molecules is limited, nucleated cells are able to escape cell death by endocytosis and by shedding of membr anes bearing C5b-9. Sublytic C5b-9 induces proto-oncogenes, activates the c ell cycle, and enhances cell survival. In addition, C5b-9 reverses the diff erentiated phenotype of postmitotic cells, such as oligodendrocytes and ske letal muscle cells. The signal transduction pathways responsible for cell c ycle activation by C5b-9 include Gi-mediated activation of extracellular si gnal-regulated kinase 1 and phosphatidylinositol 3-kinase (PI3-K). Cell sur vival enhanced by C5b-9 is mediated by the PI3-K/Akt pathway, which inhibit s apoptosis through regulation of BAD. These findings indicate that complem ent activation and membrane assembly of syblytic C5b-9 play an important ro le in inflammation by promoting cell proliferation and by rescuing apoptoti c cells.