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

Area of Science:

• Immunology
• Cell Biology
• Molecular Biology

Background:

• Complement system component C5b-9 forms transmembrane channels, typically leading to cell death.
• Nucleated cells can evade C5b-9-induced cell death through endocytosis or membrane shedding when C5b-9 levels are limited.
• Sublytic C5b-9 has been observed to influence cellular processes beyond cell lysis.

Purpose of the Study:

• To investigate the effects of sublytic C5b-9 assembly on cell membranes.
• To elucidate the signal transduction pathways involved in sublytic C5b-9-mediated cellular responses.
• To determine the role of sublytic C5b-9 in cell survival and phenotype modulation.

Main Methods:

• Cell culture models including oligodendrocytes and skeletal muscle cells.
• Analysis of cell cycle activation and proto-oncogene expression.
• Investigation of signal transduction pathways, including Gi-mediated ERK1 activation and PI3-K/Akt signaling.

Main Results:

• Sublytic C5b-9 induces proto-oncogenes, activates the cell cycle, and enhances cell survival.
• C5b-9 reverses the differentiated phenotype in postmitotic cells like oligodendrocytes and skeletal muscle cells.
• Gi-mediated ERK1 and PI3-K pathways are crucial for cell cycle activation, while PI3-K/Akt mediates enhanced cell survival by inhibiting apoptosis via BAD regulation.

Conclusions:

• Complement activation and sublytic C5b-9 membrane assembly play a significant role in inflammatory processes.
• Sublytic C5b-9 promotes cell proliferation and rescues apoptotic cells, contributing to inflammation.
• The findings highlight a novel function of complement in regulating cell fate and inflammatory responses.