SLC10A4 regulates IgE-mediated mast cell degranulation in vitro and mast cell-mediated reactions in vivo

Abstract Mast cells act as sensors in innate immunity and as effector cells in adaptive immune reactions. Here we demonstrate that SLC10A4, also referred to as the vesicular aminergic-associated transporter, VAAT, modifies mast cell degranulation. Strikingly, Slc10a4 −/− bone marrow-derived mast cel...

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Autores principales:	Hanna Pettersson, Behdad Zarnegar, Annika Westin, Viktor Persson, Christiane Peuckert, Jörgen Jonsson, Jenny Hallgren, Klas Kullander
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/741c7a5b20964df38f985281738b71f6
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spelling	oai:doaj.org-article:741c7a5b20964df38f985281738b71f62021-12-02T15:04:55ZSLC10A4 regulates IgE-mediated mast cell degranulation in vitro and mast cell-mediated reactions in vivo10.1038/s41598-017-01121-82045-2322https://doaj.org/article/741c7a5b20964df38f985281738b71f62017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01121-8https://doaj.org/toc/2045-2322Abstract Mast cells act as sensors in innate immunity and as effector cells in adaptive immune reactions. Here we demonstrate that SLC10A4, also referred to as the vesicular aminergic-associated transporter, VAAT, modifies mast cell degranulation. Strikingly, Slc10a4 −/− bone marrow-derived mast cells (BMMCs) had a significant reduction in the release of granule-associated mediators in response to IgE/antigen-mediated activation, whereas the in vitro development of mast cells, the storage of the granule-associated enzyme mouse mast cell protease 6 (mMCP-6), and the release of prostaglandin D2 and IL-6 were normal. Slc10a4-deficient mice had a strongly reduced passive cutaneous anaphylaxis reaction and a less intense itching behaviour in response to the mast cell degranulator 48/80. Live imaging of the IgE/antigen-mediated activation showed decreased degranulation and that ATP was retained to a higher degree in mast cell granules lacking SLC10A4. Furthermore, ATP was reduced by two thirds in Slc10a4 −/− BMMCs supernatants in response to IgE/antigen. We speculate that SLC10A4 affects the amount of granule-associated ATP upon IgE/antigen-induced mast cell activation, which affect the release of granule-associated mast cell mediators. In summary, SLC10A4 acts as a regulator of degranulation in vitro and of mast cell-related reactions in vivo.Hanna PetterssonBehdad ZarnegarAnnika WestinViktor PerssonChristiane PeuckertJörgen JonssonJenny HallgrenKlas KullanderNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hanna Pettersson Behdad Zarnegar Annika Westin Viktor Persson Christiane Peuckert Jörgen Jonsson Jenny Hallgren Klas Kullander SLC10A4 regulates IgE-mediated mast cell degranulation in vitro and mast cell-mediated reactions in vivo
description	Abstract Mast cells act as sensors in innate immunity and as effector cells in adaptive immune reactions. Here we demonstrate that SLC10A4, also referred to as the vesicular aminergic-associated transporter, VAAT, modifies mast cell degranulation. Strikingly, Slc10a4 −/− bone marrow-derived mast cells (BMMCs) had a significant reduction in the release of granule-associated mediators in response to IgE/antigen-mediated activation, whereas the in vitro development of mast cells, the storage of the granule-associated enzyme mouse mast cell protease 6 (mMCP-6), and the release of prostaglandin D2 and IL-6 were normal. Slc10a4-deficient mice had a strongly reduced passive cutaneous anaphylaxis reaction and a less intense itching behaviour in response to the mast cell degranulator 48/80. Live imaging of the IgE/antigen-mediated activation showed decreased degranulation and that ATP was retained to a higher degree in mast cell granules lacking SLC10A4. Furthermore, ATP was reduced by two thirds in Slc10a4 −/− BMMCs supernatants in response to IgE/antigen. We speculate that SLC10A4 affects the amount of granule-associated ATP upon IgE/antigen-induced mast cell activation, which affect the release of granule-associated mast cell mediators. In summary, SLC10A4 acts as a regulator of degranulation in vitro and of mast cell-related reactions in vivo.
format	article
author	Hanna Pettersson Behdad Zarnegar Annika Westin Viktor Persson Christiane Peuckert Jörgen Jonsson Jenny Hallgren Klas Kullander
author_facet	Hanna Pettersson Behdad Zarnegar Annika Westin Viktor Persson Christiane Peuckert Jörgen Jonsson Jenny Hallgren Klas Kullander
author_sort	Hanna Pettersson
title	SLC10A4 regulates IgE-mediated mast cell degranulation in vitro and mast cell-mediated reactions in vivo
title_short	SLC10A4 regulates IgE-mediated mast cell degranulation in vitro and mast cell-mediated reactions in vivo
title_full	SLC10A4 regulates IgE-mediated mast cell degranulation in vitro and mast cell-mediated reactions in vivo
title_fullStr	SLC10A4 regulates IgE-mediated mast cell degranulation in vitro and mast cell-mediated reactions in vivo
title_full_unstemmed	SLC10A4 regulates IgE-mediated mast cell degranulation in vitro and mast cell-mediated reactions in vivo
title_sort	slc10a4 regulates ige-mediated mast cell degranulation in vitro and mast cell-mediated reactions in vivo
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/741c7a5b20964df38f985281738b71f6
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SLC10A4 regulates IgE-mediated mast cell degranulation in vitro and mast cell-mediated reactions in vivo

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