Ra C, Kuromitsu S, Hirose T, Yasuda S, Furuichi K, Okumura K
Department of Immunology, Juntendo University, School of Medicine, Tokyo, Japan.
Int Immunol. 1993 Jan;5(1):47-54. doi: 10.1093/intimm/5.1.47.
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.
IgE高亲和力受体（FcεRI）具有四聚体结构，由一个α亚基、一个β亚基和两个通过二硫键连接的γ亚基组成，其中α亚基以高亲和力结合IgE。最近通过基因工程制备了人FcεRIα亚基胞外域的重组可溶性形式（rsFcεRIα），并证实其结合IgE的亲和力与细胞表面天然FcεRI一样高。为了分析其生物学功能，对rsFcεRIα进行了大规模制备。rsFcεRIα完全抑制IgE与细胞表面的结合，导致RBL-2H3细胞释放化学介质的现象消失。此外，在IgE致敏前将其注射到大鼠体内时，它通过特异性捕获IgE完全消除了被动皮肤过敏反应（PCA）。即使在IgE致敏后，rsFcεRIα处理也能显著降低PCA反应。最终表明，rsFcεRIα抑制IgE与人外周血嗜碱性粒细胞的结合以及它们释放组胺。在本文中，我们探讨了rsFcεRIα特异性预防IgE介导的过敏反应的能力。
