Complement (C5b-9) induces DNA synthesis in rat mesangial cells in vitro

Background The membrane attack complex C5b-9 causes injury in many forms of immune-mediated glomerular diseases characterized by mesangial cell (MC) p roliferation and inhibiting C5b-9 decreases MC proliferation in vivo. Membr ane insertion of sublytic quantities of the membrane attack complex of comp lement (C5b-9) is a potent stimulus for cell activation and the production of a variety of cytokines, growth factors, oxidants, matrix components, and other nephritogenic molecules. In vivo, a common response of MC to C5b-9-m ediated injury is cell proliferation, an event closely linked to matrix exp ansion and sclerosis. In this study, we tested the hypothesis that C5b-9 mi ght also serve as a mitogenic stimulus for MCs. Methods. Rat MCs in vitro were exposed anti-Thy1 antibody and 2% normal PVG serum (a complement source) to induce sublytic C5b-9 attack and DNA synthe sis and cell number were measured. Control MCs were exposed to antibody and C6-deficient PVG serum. Results. Sublytic C5b-9-induced injury to MCs is sufficient to induce DNA s ynthesis. Furthermore, C5b-9 augmented DNA synthesis induced by platelet-de rived growth factor (PDGF) and 5% fetal calf serum. C5b-9-induced DNA synth esis was reduced by inhibiting reactive oxygen species (ROS) with superoxid e dismutase and catalase, but not by neutralizing the mitogenic growth fact ors PDGF and basic fibroblast growth factor (bFGF). Conclusions. This study demonstrates that C5b-9 may directly increase DNA s ynthesis in cultured MCs, which are mediated in part by the release of ROS, and that C5b-9 also augments DNA synthesis induced in MCs by other known m itogens.