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

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Abstract

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.

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Acknowledgments

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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  1. Department of Neurology, School of Medicine, University of Maryland, 655 W. Baltimore Street, BRB 12-033, Baltimore, MD, 21201, USA

    Cosmin A. Tegla, Cornelia Cudrici, Snehal Patel, Richard Trippe III & Horea Rus

  2. Research Service, Veterans Administration Maryland Health Care System, Baltimore, MD, USA

    Cosmin A. Tegla & Horea Rus

  3. Department of Medicine, Division of Rheumatology and Clinical Immunology, School of Medicine, University of Maryland, Baltimore, MD, USA

    Violeta Rus & Florin Niculescu

  4. Veterans Administration Multiple Sclerosis Center of Excellence, Baltimore, MD, USA

    Horea Rus

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  1. Cosmin A. Tegla
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Correspondence to Horea Rus.

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Tegla, C.A., Cudrici, C., Patel, S. et al. Membrane attack by complement: the assembly and biology of terminal complement complexes. Immunol Res 51, 45–60 (2011). https://doi.org/10.1007/s12026-011-8239-5

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