Mechanisms of signal transduction activated by sublytic assembly of terminal complement complexes on nucleated cells.

The sublytic assembly of C5b-7, C5b-8, and C5b-9, activates membrane phospholipases through heterotrimeric G proteins and stimulates a variety of cellular activities including prostanoids, leukotrienes, and cytokines synthesis. Activation of mitotic signaling through Ras, Raf-1, ERK1, and phosphatidylinositol-3 kinase (PI3-K) was induced in B lymphocytes, endothelial, and smooth muscle cells. PI3-K activation by C5b-9 induced STAT3 phosphorylation and translocation from cytoplasm to nucleus. This complex signaling mechanism is directly involved in many biological functions such as endo- and exocytosis, cell cycle progression, activation of transcription, and protein synthesis. The key role of this signaling pathway is reflected on cell survival and proliferation in acute and chronic inflammation where complement activation is an ubiquitous event.