Sublytic complement injury does not activate NF-kappa B, or induce mitogenesis in rat mesangial cells

Sublytic complement injury to glomerular mesangial cells, mediated by the t erminal membrane attack complex of complement (C5b-9), is a potential initi ating mechanism in IgA nephropathy. Sublytic complement injury has been rep orted to result in the production of a variety of pro-inflammatory molecule s and growth factors, including many regulated by the transcription factor NF-kappa B. To determine the importance of complement injury in the pro-inf lammatory signalling which occurs in IgA nephropathy, we investigated NF-ka ppa B activation following sublytic complement injury to cultured rat glome rular mesangial cells (RMCs). A sublytic dose of rabbit anti-Thy 1.1 (THY) serum and normal human serum was selected based upon flow cytometry, chromi um-release assay, and induction of superoxide production. No significant C5 b-9-induced NF-kappa B activation was detected by electrophoretic mobility shift assays, luciferase activity of RMCs transfected with a NF-kappa B-dri ven luciferase reporter construct, nor by Northern blots for the NF-kappa B -responsive mRNA species monocyte chemoattractant protein-1 or I kappa B al pha. Furthermore, measurements of H-3 incorporation following sublytic comp lement injury showed inhibition of mesangial cell mitogenesis in comparison to the heat-inactivated serum treatment and to THY alone. The results of t his study suggest that sublytic complement injury to RMC does not directly activate NF-kappa B nor induce mesangial cell proliferation in mesangial ce lls. Other mechanisms such as IgA immune complex formation must be required to produce these events in IgA nephropathy. Copyright (C) 2000 S. Karger A G, Basel.