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

Immunol Rev. 2001 Apr:180:49-55. doi: 10.1034/j.1600-065x.2001.1800104.x.


Assembly of C5b-9 on cell membranes results in transmembrane channels and causes 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 membranes bearing C5b-9. Sublytic CSb-9 induces proto-oncogenes, activates the cell cycle, and enhances cell survival. In addition, C5b-9 reverses the differentiated phenotype of postmitotic cells, such as oligodendrocytes and skeletal muscle cells. The signal transduction pathways responsible for cell cycle activation by CSb-9 include Gi-mediated activation of extracellular signal-regulated kinase 1 and phosphatidylinositol 3-kinase (PI3-K). Cell survival enhanced by C5b-9 is mediated by the PI3-K/Akt pathway, which inhibits apoptosis through regulation of BAD. These findings indicate that complement activation and membrane assembly of sublytic C5b-9 play an important role in inflammation by promoting cell proliferation and by rescuing apoptotic cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Carrier Proteins / physiology
  • Cell Cycle / physiology*
  • Cell Differentiation / physiology
  • Cell Membrane Permeability
  • Complement Membrane Attack Complex / physiology*
  • Endocytosis
  • Gene Expression Regulation / physiology
  • Humans
  • MAP Kinase Signaling System / physiology
  • Mitochondria / physiology
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / physiology
  • Necrosis
  • Phosphatidylinositol 3-Kinases / physiology
  • Protein Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / physiology
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins c-bcl-2 / physiology
  • Proto-Oncogenes
  • Retinoblastoma Protein / physiology
  • bcl-2-Associated X Protein
  • bcl-Associated Death Protein
  • bcl-X Protein


  • BAD protein, human
  • BCL2L1 protein, human
  • Carrier Proteins
  • Complement Membrane Attack Complex
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Retinoblastoma Protein
  • bcl-2-Associated X Protein
  • bcl-Associated Death Protein
  • bcl-X Protein
  • AKT1 protein, human
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases