Immunologic Research

, 51:45 | Cite as

Membrane attack by complement: the assembly and biology of terminal complement complexes

  • Cosmin A. Tegla
  • Cornelia Cudrici
  • Snehal Patel
  • Richard TrippeIII
  • Violeta Rus
  • Florin Niculescu
  • Horea Rus


Complement system activation plays an important role in both innate and acquired immunity. Activation of the complement and the subsequent formation of C5b-9 channels (the membrane attack complex) on the cell membranes lead to cell death. However, when the number of channels assembled on the surface of nucleated cells is limited, sublytic C5b-9 can induce cell cycle progression by activating signal transduction pathways and transcription factors and inhibiting apoptosis. This induction by C5b-9 is dependent upon the activation of the phosphatidylinositol 3-kinase/Akt/FOXO1 and ERK1 pathways in a Gi protein-dependent manner. C5b-9 induces sequential activation of CDK4 and CDK2, enabling the G1/S-phase transition and cellular proliferation. In addition, it induces RGC-32, a novel gene that plays a role in cell cycle activation by interacting with Akt and the cyclin B1-CDC2 complex. C5b-9 also inhibits apoptosis by inducing the phosphorylation of Bad and blocking the activation of FLIP, caspase-8, and Bid cleavage. Thus, sublytic C5b-9 plays an important role in cell activation, proliferation, and differentiation, thereby contributing to the maintenance of cell and tissue homeostasis.


C5b-9 terminal complement complex Membrane attack complex Cell cycle Signal transduction Transcriptional regulation Apoptosis 



We thank Dr. Deborah McClellan for editing this manuscript. This work was supported in part by US Public Health Grant RO1 NS42011 (to H.R.) and a Veterans Administration Merit Award (to H.R.).


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Cosmin A. Tegla
    • 1
    • 2
  • Cornelia Cudrici
    • 1
  • Snehal Patel
    • 1
  • Richard TrippeIII
    • 1
  • Violeta Rus
    • 3
  • Florin Niculescu
    • 3
  • Horea Rus
    • 1
    • 2
    • 4
  1. 1.Department of Neurology, School of MedicineUniversity of MarylandBaltimoreUSA
  2. 2.Research ServiceVeterans Administration Maryland Health Care SystemBaltimoreUSA
  3. 3.Department of Medicine, Division of Rheumatology and Clinical Immunology, School of MedicineUniversity of MarylandBaltimoreUSA
  4. 4.Veterans Administration Multiple Sclerosis Center of ExcellenceBaltimoreUSA

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