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

Abstract

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.

NF-κB and Enhancer-binding CREB Protein Scaffolded by CREB-binding Protein (CBP)/p300 Proteins Regulate CD59 Protein Expression to Protect Cells from Complement Attack

“…Deficient or reduced CD59 expression in pathogens or host cells may lead to the direct lysis of invading pathogens or autologous cells in various diseases, such as autoimmune hemocytopenia and systemic lupus erythematosus (4,5). In contrast, high CD59 expression in abnormal host cells leads to the incapability of the complement system to destroy target cells and triggers comprehensive downstream pro-cell survival signaling (6). Therefore, these findings highlight the need to decipher the regulation of CD59 in human disorders.…”

Experimental membranous nephropathy redux

“…1). Nucleated cells require multiple C5b-9 lesions for lysis, whereas at lower doses C5b-9 induces sublethal (sublytic) injury (83,94,116). The response of a cell, including the GEC, to sublytic doses of C5b-9 attack is not simply due to disruption of the plasma membrane but rather to the activation of specific signaling pathways.…”

Non-proteolytic, Receptor/Ligand Interactions Associate Cellular Membrane Type-1 Matrix Metalloproteinase with the Complement Component C1q

“…Upon binding to immunoglobulin-coated targets, C1q undergoes a conformational change that initiates a highly specific intramolecular proteolytic activation of the C1r(2)-C1s(2) tetramer. These events are followed by complement propagation, which includes the deposition of opsonins on the activating cell surface, the release of anaphylatoxins, and the formation of the terminal cytolytic membrane attack complex, which eventually leads to cell death (10,12,20). Another important, but less well understood, function of C1q is the induction of cell-specific functional responses mediated by its binding to receptors present on endothelial cells, dendritic cells, platelets, monocytes, lymphocytes, and leukocytes (15,21).…”