Complement C5b-9

C5b-9, also known as membrane attack complex (MAC) or terminal complement complex (TCC), is a complex of proteins generated on the surface of pathogen cell membranes as a result of the activation of the host's complement system. C5b-9 is composed of C5b, C6, C7, C8, and several C9 molecules. In the assembly of the C5b-9, firstly, activated C5b binds to C6 to generate a C5b-6 complex; next, C7 bind to C5b-6 complex to form the C5b-6-7 complex; then the C5b-6-7 complex bind to C8 and form the C5b-6-7-8 complex; finally, C5b-6-7-8 binds to C9 and form the C5b-9 complex.

Typically, the assembly of C5b-9 on cell membranes leads to transmembrane channels and results in cell death. However, when the C5b-9 molecules are insufficient, nucleated cells can escape cell death through endocytosis and via shedding of membranes bearing C5b-9. Meanwhile, sublytic C5b-9 leads to proto-oncogenes, activates the cell cycle, and promotes cell survival. There are two signal transduction pathways responsible for cell cycle activation by C5b-9, which are phosphatidylinositol 3-kinase (PI3-K) and Gi-mediated activation of extracellular signal-regulated kinase 1. In addition, complement activation and membrane assembly of sublytic C5b-9 act as an essential part of inflammation by enhancing cell proliferation and by rescuing apoptotic cells.

Fig. 1 Activation and regulation of complement pathways.¹

Reference

1. Fishelson, Zvi, and Michael Kirschfink. "Complement C5b-9 and cancer: mechanisms of cell damage, cancer counteractions, and approaches for intervention." Frontiers in immunology 10 (2019): 752.