Antibody to FcεRIα Suppresses Immunoglobulin E Binding to High-Affinity Receptor I in Allergic Inflammation
Yonsei Medical Journal
; : 1412-1419, 2016.
Article
em En
| WPRIM
| ID: wpr-143184
Biblioteca responsável:
WPRO
ABSTRACT
PURPOSE:
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. MATERIALS ANDMETHODS:
Fab fragment antibodies, which lack the Fc domain, with high affinity and specificity for FcεRIα and effective inhibitory activity against IgE-FcεRI binding were screened. IgE-induced histamine, β-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 FcεRIα (KD=4 nM) and inhibited histamine, β-hexosaminidase and Ca2+ release in a concentration-dependent manner in hFcεRI-expressing cells. In hFcεRIα-expressing mice, dye leakage was higher in the PCA group than in controls, but decreased after NPB311 treatment. NPB311 could form a complex with FcεRIα and inhibit the release of inflammation mediators.CONCLUSION:
Our approach for producing anti-FcεRIα Fab fragment antibody NPB311 may enable clinical application to a therapeutic pathway in IgE/FcεRI-mediated diseases.Palavras-chave
Texto completo:
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Índice:
WPRIM
Assunto principal:
Pele
/
Basófilos
/
Imunoglobulina E
/
Imunoglobulinas
/
Ensaio de Imunoadsorção Enzimática
/
Anafilaxia Cutânea Passiva
/
Histamina
/
Sensibilidade e Especificidade
/
Mediadores da Inflamação
/
Hipersensibilidade Imediata
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Yonsei Medical Journal
Ano de publicação:
2016
Tipo de documento:
Article