Modulation of murine and human interferon-γ receptor expression by their ligands or phorbol ester

Abstract

IFN-γ receptor expression on murine leukaemic L1210-cells has been studied. With the help of a transfected cell-line expressing the heterologous human receptor it was possible to discern receptor-specific properties like internalization from those regulating their expression on the surface. Recombinant IFN-γ binds specifically to its homologous receptor at 4°C and is rapidly internalized at physiologic temperatures. For this effect to occur, ligand binding to its receptor at 37°C is necessary and sufficient. This notion is confirmed since a reduction in the number of heterologous human IFN-γ receptors on the murine cell surface occurred exclusively after treatment with human IFN-γ. Even weak doses of ligand, insufficient to occupy all receptors, led to a pronounced disappearance of binding sites. However, both receptors are simultaneously up-regulated in the presence of TPA, indicating a separate pathway which is not species-specific. Our findings imply that similar elements of the intracellular signal transduction machinery are involved in the control of MuIFN-γ and HuIFN-γ receptor expression. The results indicate also that factors involved in binding, internalization, and regulation of receptor gene expression are not species-specific.