Expression of a functional high-affinity IgG receptor, Fc gamma RI, on human mast cells: Up-regulation by IFN-gamma

Biologically relevant activation of human mast cells through Fc receptors i s believed to occur primarily through the high-affinity IgE receptor Fc eps ilon RI, However, the demonstration in animal models that allergic reaction s do not necessarily require Ag-specific IgE, nor the presence of a functio nal IgE receptor, and the clinical occurrence of some allergic reactions in situations where Ag-specific IgE appears to be lacking, led us to examine the hypothesis that human mast cells might express the high-affinity IgG re ceptor Fc gamma RI and in turn be activated through aggregation of this rec eptor. We thus first determined by RT-PCR that resting human mast cells exh ibit minimal message for Fc gamma RI, We next found that IFN-gamma up regul ated the expression of Fc gamma RI. This was confirmed by flow cytometry, w here Fc gamma RI expression on human mast cells was increased from similar to 2 to 44% by IFN-gamma exposure. Fc epsilon RI, Fc gamma RII, and Fc gamm a RIII expression was not affected. Scatchard plots were consisted with the se data where the average binding sites for monomeric IgG1 (K-a = 4-5 x 10( 8) M-1) increased from similar to 2,400 to 12,100-17,300 per cell. aggregat ion of Fc gamma RI on human mast cells, and only after IFN-gamma exposure, led to significant degranulation as evidenced by histamine release (24.5 +/ - 4.4%): and up-regulation of mRNA expression for specific cytokines includ ing TNF-alpha, GM-CSF, IL-3 and IL-13, These findings thus suggest another mechanism by which human mast cells may be recruited into the inflammatory processes associated with some immunologic and infectious diseases.