Soluble human high-affinity receptor for IgE abrogates the IgE-mediated allergic reaction

Abstract

The high-affinity receptor for IgE (FcεRI) has a tetrameric structure composed of oneα, one β, and two disulfide-linked γ subunits, of which the α subunit binds IgE with high affinity. A recombinant soluble form of the ectodomain of the human FcεRIα subunit (rsFcεRIα) was recently generated by gene engineering and was verified to bind IgE with an affinity as high as that of native FcεRI on the cell surface. rsFcεRIα was prepared on a large scale in order to analyze its biological function. rsFcεRIα completely inhibited IgE binding to the cell surface, resulting in abrogation of the chemical mediator release from RBL-2H3 cells. Furthermore it completely abolished the passive cutaneous anaphylaxis (PCA) response by trapping IgE specifically when itwas administered into rats prior to IgE sensltizatlon. Even after IgE sensitizatlon, treatment of rsFcεRIα substantially reduced the PCA response. It was finally shown that rsFcεRIα inhibited IgE binding to human peripheral blood basophils and the histamine release from them. In this paper we address the ability of rsFcεRIα to specifically prevent the IgE-mediated allergic reaction.