Dataset Information
Antibody to Fc?RI? Suppresses Immunoglobulin E Binding to High-Affinity Receptor I in Allergic Inflammation.
Ontology highlight
ABSTRACT: Purpose
High-affinity receptor I (Fc?RI) on mast cells and basophils plays a key role in the immunoglobulin E (IgE)-mediated type I hypersensitivity mediated by allergen cross-linking of the specific IgE-Fc?RI complex. Thus, prevention of IgE binding to Fc?RI on these cells is an effective therapy for allergic disease. We have developed a strategy to disrupt IgE binding to Fc?RI using an antibody targeting Fc?RI?.Materials and methods
Fab fragment antibodies, which lack the Fc domain, with high affinity and specificity for Fc?RI? and effective inhibitory activity against IgE-Fc?RI binding were screened. IgE-induced histamine, ?-hexosaminidase and Ca²? release in basophils were determined by ELISA. A B6.Cg-Fcer1a(tm1Knt) Tg(FCER1A)1Bhk/J mouse model of passive cutaneous anaphylaxis (PCA) was used to examine the inhibitory effect of NPB311 on allergic skin inflammation.Results
NPB311 exhibited high affinity to human Fc?RI? (KD=4 nM) and inhibited histamine, ?-hexosaminidase and Ca²? release in a concentration-dependent manner in hFc?RI-expressing cells. In hFc?RI?-expressing mice, dye leakage was higher in the PCA group than in controls, but decreased after NPB311 treatment. NPB311 could form a complex with Fc?RI? and inhibit the release of inflammation mediators.Conclusion
Our approach for producing anti-Fc?RI? Fab fragment antibody NPB311 may enable clinical application to a therapeutic pathway in IgE/Fc?RI-mediated diseases.
SUBMITTER: Hong JY
PROVIDER: S-EPMC5011273 | biostudies-literature | 2016 Nov
REPOSITORIES: biostudies-literature
Publications
Antibody to FcεRIα Suppresses Immunoglobulin E Binding to High-Affinity Receptor I in Allergic Inflammation.
Yonsei medical journal 20161101 6
<h4>Purpose</h4>High-affinity receptor I (FcεRI) on mast cells and basophils plays a key role in the immunoglobulin E (IgE)-mediated type I hypersensitivity mediated by allergen cross-linking of the specific IgE-FcεRI complex. Thus, prevention of IgE binding to FcεRI on these cells is an effective therapy for allergic disease. We have developed a strategy to disrupt IgE binding to FcεRI using an antibody targeting FcεRIα.<h4>Materials and methods</h4>Fab fragment antibodies, which lack the Fc do ...[more]