Abstract
ABSTRACT
Expression and diverse functions of MHC class I related neonatal Fc receptor in different tissues is continually reported. To contribute to the understanding of how the receptor functions according to cell type, we investigated the expression and ligands binding properties of FcRn in human immune cells and hepatocytes. Here, we report that heterodimeric FcRn is expressed in these cells as evidenced by RT-PCR, Western immunoblottting and flow cytometry. The receptor expression is shown to be predominantly intracellular as compared to that on the surface. Our report on human hepatocytes and monocytic K-562 cells is for the first time. In addition, the human hepatic cell lines were shown to express FcgRII but no evidence of FcgRI and FcgRIII. Our pH dependent cell binding assays have demonstrated increased binding of hIgG and HSA to membrane-bound hFcRn at acidic pH in these cells and the pH dependent binding of IgG is Fc mediated. The increased binding of IgG and HSA at acidic pH is completely mediated by FcRn as shown by anti-FcRn inhibition and not affected by isotype goat IgG. It was found that IgG and HSA bind to the membrane-FcRn independently of each other and this is the first report of pH dependent HSA binding to a membrane-bound hFcRn. Moreover, we have shown that anti-inflammatory substances such as both naturally occurring and synthetic glucocorticoids, and L-thyroxine clearly downregulate the FcRn expression in human monocytic U-937 and hepatic cell lines.