Soluble human high-affinity receptor for IgE abrogates the IgE-mediated allergic reaction.
The high-affinity receptor for IgE (Fc epsilon RI) has a tetrameric structure structure composed of one alpha, one beta, and two disulfide-linked gamma subunits, of which the alpha subunit binds IgE with high affinity. A recombinant soluble form of the ectodomain of the human Fc epsilon RI alpha subunit (rsFc epsilon RI alpha) was recently generated by gene engineering and was verified to bind IgE with an affinity as high as that of native Fc epsilon RI on the cell surface. rsFc epsilon RI alpha was prepared on a large scale in order to analyze its biological function. rsFc epsilon RI alpha 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 it was administered into rats prior to IgE sensitization. Even after IgE sensitization, treatment of rsFc epsilon RI alpha substantially reduced the PCA response. It was finally shown that rsFc epsilon RI alpha inhibited IgE binding to human peripheral blood basophils and the histamine release from them. In this paper we address the ability of rsFc epsilon RI alpha to specifically prevent the IgE-mediated allergic reaction.
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Department of Immunology, Juntendo University, School of Medicine, Tokyo, Japan.
Kuromitsu
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Hirose
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Yasuda
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Furuichi
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Okumura
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D000818:Animals; D001491:Basophils / Q000378:metabolism; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003876:Dermatitis, Atopic / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D004591:Electrophoresis, Polyacrylamide Gel; D006636:Histamine Release; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology* / Q000378:metabolism; D007275:Injections, Intravenous; D008925:Mites / Q000276:immunology; D010323:Passive Cutaneous Anaphylaxis / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017455:Receptors, IgE / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D012397:Rosette Formation; D012701:Serotonin / Q000096:biosynthesis; D014162:Transfection; D014611:Vaccination
D017455:Receptors, IgE; D011994:Recombinant Proteins; D012701:Serotonin; D007073:Immunoglobulin E