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Negative Regulation of FcεRI-mediated Degranulation by CD81

Signaling through the high affinity receptor for immunoglobulin E (FcεRI) results in the coordinate activation of tyrosine kinases before calcium mobilization. Receptors capable of interfering with the signaling of antigen receptors, such as FcεRI, recruit tyrosine and inositol phosphatases that res...

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Autores principales: Fleming, Tony J., Donnadieu, Emmanuel, Song, Chang Ho, Laethem, Francois Van, Galli, Stephen J., Kinet, Jean-Pierre
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1997
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2199099/
https://www.ncbi.nlm.nih.gov/pubmed/9334370
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author Fleming, Tony J.
Donnadieu, Emmanuel
Song, Chang Ho
Laethem, Francois Van
Galli, Stephen J.
Kinet, Jean-Pierre
author_facet Fleming, Tony J.
Donnadieu, Emmanuel
Song, Chang Ho
Laethem, Francois Van
Galli, Stephen J.
Kinet, Jean-Pierre
author_sort Fleming, Tony J.
collection PubMed
description Signaling through the high affinity receptor for immunoglobulin E (FcεRI) results in the coordinate activation of tyrosine kinases before calcium mobilization. Receptors capable of interfering with the signaling of antigen receptors, such as FcεRI, recruit tyrosine and inositol phosphatases that results in diminished calcium mobilization. Here, we show that antibodies recognizing CD81 inhibit FcεRI-mediated mast cell degranulation but, surprisingly, without affecting aggregation-dependent tyrosine phosphorylation, calcium mobilization, or leukotriene synthesis. Furthermore, CD81 antibodies also inhibit mast cell degranulation in vivo as measured by reduced passive cutaneous anaphylaxis responses. These results reveal an unsuspected calcium-independent pathway of antigen receptor regulation, which is accessible to engagement by membrane proteins and on which novel therapeutic approaches to allergic diseases could be based.
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spelling pubmed-21990992008-04-16 Negative Regulation of FcεRI-mediated Degranulation by CD81 Fleming, Tony J. Donnadieu, Emmanuel Song, Chang Ho Laethem, Francois Van Galli, Stephen J. Kinet, Jean-Pierre J Exp Med Article Signaling through the high affinity receptor for immunoglobulin E (FcεRI) results in the coordinate activation of tyrosine kinases before calcium mobilization. Receptors capable of interfering with the signaling of antigen receptors, such as FcεRI, recruit tyrosine and inositol phosphatases that results in diminished calcium mobilization. Here, we show that antibodies recognizing CD81 inhibit FcεRI-mediated mast cell degranulation but, surprisingly, without affecting aggregation-dependent tyrosine phosphorylation, calcium mobilization, or leukotriene synthesis. Furthermore, CD81 antibodies also inhibit mast cell degranulation in vivo as measured by reduced passive cutaneous anaphylaxis responses. These results reveal an unsuspected calcium-independent pathway of antigen receptor regulation, which is accessible to engagement by membrane proteins and on which novel therapeutic approaches to allergic diseases could be based. The Rockefeller University Press 1997-10-20 /pmc/articles/PMC2199099/ /pubmed/9334370 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Fleming, Tony J.
Donnadieu, Emmanuel
Song, Chang Ho
Laethem, Francois Van
Galli, Stephen J.
Kinet, Jean-Pierre
Negative Regulation of FcεRI-mediated Degranulation by CD81
title Negative Regulation of FcεRI-mediated Degranulation by CD81
title_full Negative Regulation of FcεRI-mediated Degranulation by CD81
title_fullStr Negative Regulation of FcεRI-mediated Degranulation by CD81
title_full_unstemmed Negative Regulation of FcεRI-mediated Degranulation by CD81
title_short Negative Regulation of FcεRI-mediated Degranulation by CD81
title_sort negative regulation of fcεri-mediated degranulation by cd81
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2199099/
https://www.ncbi.nlm.nih.gov/pubmed/9334370
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