Monocyte chemoattractant protein (MCP)-1 production via functionally reconstituted Fcα receptor (CD89) on glomerular mesangial cells

Background: Fc alpha receptor (FcalphaR; CD89) is the receptor for Fc portion of IgA in various cells, and displays various immunological responses on binding. It is important to analyze the mesangial functions via FcaR in the pathogenesis of IgA nephropathy. However, it is still controversial whether FcaR is expressed on mesangial cells. To assess biological functions of FcaR on the mesangial cells, we established mesangial transfectants that expressed FcaR with or without FcRgamma chain that is a common signaling molecule of FcRs. The production of monocyte chemoattractant protein-1 (MCP-1) by mesangial cells is known to contribute to cellular infiltration into glomeruli and subsequent glomerular injuries. Methods: Murine mesangial cell lines (SV40 MES 13) were transfected with cDNA of the human FcaR. Furthermore, we co-transfected some of the FcaR transfectants with cDNA of human FcRgamma chain. The tyrosine phosphorylation of the infra-mesangial proteins after FcaR cross-linking was examined by immunoprecipitation. MCP-1 production from each transfectant stimulated with heat aggregated IgA was determined by sandwich ELISA. Results: Two kinds of mesangial transfectants stably expressed human FcaR with or without FcRgamma chain (FcalphaR(+), FcalphaR(+)/gamma(+)). Phosphorylation of FcRgamma chain and syk kinase was detected in FcalphaR(+) and FcalphaR(+)/gamma(+) cells, but not in untransfected cells. Aggregated IgA induced significantly higher MCP-1 production in FcalphaR(+)/gamma(+) than those in FcalphaR(+) or untransfected control. Conclusion: Present study demonstrated that FcalphaR and FcRgamma chain could be reconstituted in mesangial cells and mediated MCP-1 production by aggregated IgA in a dose-dependent manner. Current data would argue that FcalphaR can be activated in mesangial cells through their own machinery, although underlying mechanisms for FcalphaR induction in mesangial cells remain unclear.