Terminal complement complex C5b-9 stimulates mitogenesis in 3T3 cells.
The membrane attack complex of complement (MAC) can induce reversible changes in cell membrane permeability resulting in significant but transient intracellular ionic changes in the absence of cell lysis. Because ion fluxes and cytosolic ionic changes are integral steps in the signaling cascade initiated when growth factors bind to their receptors, we hypothesized that the MAC-induced reversible changes in membrane permeability could stimulate cell proliferation. Using purified terminal complement components we have documented a mitogenic effect of the MAC for quiescent murine 3T3 cells. The MAC enhances the mitogenic effects of serum and PDGF, and also stimulates cell proliferation in the absence of other exogenous growth factors. MAC-induced mitogenesis represents a novel effect of the terminal complement complex that could contribute to focal tissue repair or pathological cell proliferation locally at sites of complement activation.
Halperin
J A
JA
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Taratuska
A
A
Nicholson-Weller
A
A
D016475:3T3 Cells; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects*; D015938:Complement Membrane Attack Complex / Q000494:pharmacology*; D003165:Complement System Proteins / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D051379:Mice; D008934:Mitogens / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors
D015938:Complement Membrane Attack Complex; D008934:Mitogens; D010982:Platelet-Derived Growth Factor; D003165:Complement System Proteins; D002118:Calcium; D013936:Thymidine