Abstract
Background : One of the most critical findings in patients with IgA nephropathy is glomerular mesangial deposition of IgA (IgAl). It is still unknown whether the activation of mesangial cells is directly triggered by IgA. Fc alpha receptor (FcαR) is the major receptor for binding of IgA in various cells, and displays various immunological responses on binding. There is controversy as to whether FcαR is expressed on mesangial cells. However, it is important to analyze the mesangial functions via FcαR in the pathogenesis of IgA nephropathy. To assess biological functions of FcαR on the mesangial cells, the author established mesangial transfectants which expressed FcαR and FcRγ chain. Methods : Murine mesangial cell lines (SV40 MES 13) were transfected with cDNA of human FcαR. Furthermore, I co-transfected some of the FcαR transfectants with cDNA of the human FcRγ chain which is known as a common signaling molecule of FcRs. The tyrosine phosphorylation of the intra-mesangial proteins in FcαR cross-linking was examined by immunoprecipitation. Amounts of monocyte chemoattractant protein (MCP-1) from each transfectant stimulated with heat aggregated IgA was determined by sandwich ELISA.
Results : The author generated two kinds of mesangial transfectants which stably expressed human FcαR with or without FcRγ chain (F/Fγ cells). Tyrosine phosphorylation of FcRγ chain and syk kinase was detected in F and Fγ cells, but not in untransfected cells. The secretion of MCP-1 was elicited by stimulation with aggregated IgA in F and Fγ cells in a dose-dependent manner. Moreover, MCP-1 secretion in Fγ cells was significantly higher than that in F cells. Interestingly, more MCP-1 was produced from F cells under stimulation than from untransfected cells.
Conclusion : The author confirmed that mesangial cells had the potential for cell-activation with FcαR cross-linking. Furthermore, these transfectants displayed functional output with aggregated IgA. It appears that the activation mechanisms were efficiently controlled by association of the FcRγ chain, and that FcαR with the FcRγ chain may contribute to the mesangial response to IgA deposition.
