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Lyn Is Essential for Fcγ Receptor III–Mediated Systemic Anaphylaxis but Not for the Arthus Reaction
The Src family kinase Lyn initiates intracellular signal transduction by associating with a variety of immune receptors such as antigen receptor on B cells and high-affinity Fc receptor (FcR) for immunoglobulin Ig(E) (FcεRI) on mast cells. Involvement of Lyn in the IgE-mediated immediate-type hypers...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2001
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193394/ https://www.ncbi.nlm.nih.gov/pubmed/11238587 |
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author | Yuasa, Takae Ono, Masao Watanabe, Takeshi Takai, Toshiyuki |
author_facet | Yuasa, Takae Ono, Masao Watanabe, Takeshi Takai, Toshiyuki |
author_sort | Yuasa, Takae |
collection | PubMed |
description | The Src family kinase Lyn initiates intracellular signal transduction by associating with a variety of immune receptors such as antigen receptor on B cells and high-affinity Fc receptor (FcR) for immunoglobulin Ig(E) (FcεRI) on mast cells. Involvement of Lyn in the IgE-mediated immediate-type hypersensitivity is well documented, but the physiological significance of Lyn in IgG-dependent, type III low-affinity FcR for IgG (FcγRIII)-mediated responses is largely unknown. In this study, we generated a double-mutant mouse strain deficient in both type II FcR for IgG (FcγRIIB) and Lyn to exclude any involvement of inhibitory signaling by FcγRIIB, which otherwise downregulates FcγRIII-mediated cellular responses. FcγRIIB-deficient but Lyn-sufficient mice served as controls. The Lyn deficiency attenuated IgG-mediated systemic anaphylaxis in vivo, and significantly reduced calcium mobilization and degranulation responses of bone marrow–derived mast cells (BMMCs) in vitro. However, we found that either interleukin 4 or tumor necrosis factor α release by BMMCs was comparable to that from Lyn-deficient and control mice, and the reverse-passive Arthus reaction was equally induced in both mutant mice, indicating that Lyn is not involved in the onset of the IgG-mediated, FcγRIII-dependent late phase responses of mast cells. These findings provide us with insight into distinct signaling mechanisms in mast cells underlying the development of diverse pathologies as well as a therapeutic potential for selective treatment of allergic disorders. |
format | Text |
id | pubmed-2193394 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2001 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21933942008-04-14 Lyn Is Essential for Fcγ Receptor III–Mediated Systemic Anaphylaxis but Not for the Arthus Reaction Yuasa, Takae Ono, Masao Watanabe, Takeshi Takai, Toshiyuki J Exp Med Original Article The Src family kinase Lyn initiates intracellular signal transduction by associating with a variety of immune receptors such as antigen receptor on B cells and high-affinity Fc receptor (FcR) for immunoglobulin Ig(E) (FcεRI) on mast cells. Involvement of Lyn in the IgE-mediated immediate-type hypersensitivity is well documented, but the physiological significance of Lyn in IgG-dependent, type III low-affinity FcR for IgG (FcγRIII)-mediated responses is largely unknown. In this study, we generated a double-mutant mouse strain deficient in both type II FcR for IgG (FcγRIIB) and Lyn to exclude any involvement of inhibitory signaling by FcγRIIB, which otherwise downregulates FcγRIII-mediated cellular responses. FcγRIIB-deficient but Lyn-sufficient mice served as controls. The Lyn deficiency attenuated IgG-mediated systemic anaphylaxis in vivo, and significantly reduced calcium mobilization and degranulation responses of bone marrow–derived mast cells (BMMCs) in vitro. However, we found that either interleukin 4 or tumor necrosis factor α release by BMMCs was comparable to that from Lyn-deficient and control mice, and the reverse-passive Arthus reaction was equally induced in both mutant mice, indicating that Lyn is not involved in the onset of the IgG-mediated, FcγRIII-dependent late phase responses of mast cells. These findings provide us with insight into distinct signaling mechanisms in mast cells underlying the development of diverse pathologies as well as a therapeutic potential for selective treatment of allergic disorders. The Rockefeller University Press 2001-03-05 /pmc/articles/PMC2193394/ /pubmed/11238587 Text en © 2001 The Rockefeller University Press 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 | Original Article Yuasa, Takae Ono, Masao Watanabe, Takeshi Takai, Toshiyuki Lyn Is Essential for Fcγ Receptor III–Mediated Systemic Anaphylaxis but Not for the Arthus Reaction |
title | Lyn Is Essential for Fcγ Receptor III–Mediated Systemic Anaphylaxis but Not for the Arthus Reaction |
title_full | Lyn Is Essential for Fcγ Receptor III–Mediated Systemic Anaphylaxis but Not for the Arthus Reaction |
title_fullStr | Lyn Is Essential for Fcγ Receptor III–Mediated Systemic Anaphylaxis but Not for the Arthus Reaction |
title_full_unstemmed | Lyn Is Essential for Fcγ Receptor III–Mediated Systemic Anaphylaxis but Not for the Arthus Reaction |
title_short | Lyn Is Essential for Fcγ Receptor III–Mediated Systemic Anaphylaxis but Not for the Arthus Reaction |
title_sort | lyn is essential for fcγ receptor iii–mediated systemic anaphylaxis but not for the arthus reaction |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193394/ https://www.ncbi.nlm.nih.gov/pubmed/11238587 |
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