Pannexin-1 Channels Are Essential for Mast Cell Degranulation Triggered During Type I Hypersensitivity Reactions
Mast cells (MCs) release pro-inflammatory mediators through a process called degranulation response. The latter may be induced by several conditions, including antigen recognition through immunoglobulin E (IgE) or “cross-linking,” classically associated with Type I hypersensitivity reactions. Early...
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Frontiers Media S.A.
2019-11-01
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Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.02703/full |
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doaj-6913c62c86054f8a89dfa20dd193aa8e |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Paloma A. Harcha Paloma A. Harcha Ximena López Ximena López Pablo J. Sáez Pablo J. Sáez Pablo J. Sáez Paola Fernández Iván Barría Agustín D. Martínez Juan C. Sáez Juan C. Sáez |
spellingShingle |
Paloma A. Harcha Paloma A. Harcha Ximena López Ximena López Pablo J. Sáez Pablo J. Sáez Pablo J. Sáez Paola Fernández Iván Barría Agustín D. Martínez Juan C. Sáez Juan C. Sáez Pannexin-1 Channels Are Essential for Mast Cell Degranulation Triggered During Type I Hypersensitivity Reactions Frontiers in Immunology inflammation immune cells ovalbumin pannexon degranulation histamine |
author_facet |
Paloma A. Harcha Paloma A. Harcha Ximena López Ximena López Pablo J. Sáez Pablo J. Sáez Pablo J. Sáez Paola Fernández Iván Barría Agustín D. Martínez Juan C. Sáez Juan C. Sáez |
author_sort |
Paloma A. Harcha |
title |
Pannexin-1 Channels Are Essential for Mast Cell Degranulation Triggered During Type I Hypersensitivity Reactions |
title_short |
Pannexin-1 Channels Are Essential for Mast Cell Degranulation Triggered During Type I Hypersensitivity Reactions |
title_full |
Pannexin-1 Channels Are Essential for Mast Cell Degranulation Triggered During Type I Hypersensitivity Reactions |
title_fullStr |
Pannexin-1 Channels Are Essential for Mast Cell Degranulation Triggered During Type I Hypersensitivity Reactions |
title_full_unstemmed |
Pannexin-1 Channels Are Essential for Mast Cell Degranulation Triggered During Type I Hypersensitivity Reactions |
title_sort |
pannexin-1 channels are essential for mast cell degranulation triggered during type i hypersensitivity reactions |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2019-11-01 |
description |
Mast cells (MCs) release pro-inflammatory mediators through a process called degranulation response. The latter may be induced by several conditions, including antigen recognition through immunoglobulin E (IgE) or “cross-linking,” classically associated with Type I hypersensitivity reactions. Early in this reaction, Ca2+ influx and subsequent increase of intracellular free Ca2+ concentration are essential for MC degranulation. Several membrane channels that mediate Ca2+ influx have been proposed, but their role remains elusive. Here, we evaluated the possible contribution of pannexin-1 channels (Panx1 Chs), well-known as ATP-releasing channels, in the increase of intracellular Ca2+ triggered during cross-linking reaction of MCs. The contribution of Panx1 Chs in the degranulation response was evaluated in MCs from wild type (WT) and Panx1 knock out (Panx1−/−) mice after anti-ovalbumin (OVA) IgE sensitization. Notably, the degranulation response (toluidine blue and histamine release) was absent in Panx1−/− MCs. Moreover, WT MCs showed a rapid and transient increase in Ca2+ signal followed by a sustained increase after antigen stimulation. However, the sustained increase in Ca2+ signal triggered by OVA was absent in Panx1−/− MCs. Furthermore, OVA stimulation increased the membrane permeability assessed by dye uptake, a prevented response by Panx1 Ch but not by connexin hemichannel blockers and without effect on Panx1−/− MCs. Interestingly, the increase in membrane permeability of WT MCs was also prevented by suramin, a P2 purinergic inhibitor, suggesting that Panx1 Chs act as ATP-releasing channels impermeable to Ca2+. Accordingly, stimulation with exogenous ATP restored the degranulation response and sustained increase in Ca2+ signal of OVA stimulated Panx1−/− MCs. Moreover, opening of Panx1 Chs in Panx1 transfected HeLa cells increased dye uptake and ATP release but did not promote Ca2+ influx, confirming that Panx1 Chs permeable to ATP are not permeable to Ca2+. These data strongly suggest that during antigen recognition, Panx1 Chs contribute to the sustained Ca2+ signal increase via release of ATP that activates P2 receptors, playing a critical role in the sequential events that leads to degranulation response during Type I hypersensitivity reactions. |
topic |
inflammation immune cells ovalbumin pannexon degranulation histamine |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2019.02703/full |
work_keys_str_mv |
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doaj-6913c62c86054f8a89dfa20dd193aa8e2020-11-25T02:04:09ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-11-011010.3389/fimmu.2019.02703485845Pannexin-1 Channels Are Essential for Mast Cell Degranulation Triggered During Type I Hypersensitivity ReactionsPaloma A. Harcha0Paloma A. Harcha1Ximena López2Ximena López3Pablo J. Sáez4Pablo J. Sáez5Pablo J. Sáez6Paola Fernández7Iván Barría8Agustín D. Martínez9Juan C. Sáez10Juan C. Sáez11Departamento de Fisiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, ChileFacultad de Ciencias, Instituto de Neurociencias and Centro Interdisciplinario de Neurociencias de Valparaíso, Universidad de Valparaíso, Valparaíso, ChileDepartamento de Fisiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, ChileFacultad de Ciencias, Instituto de Neurociencias and Centro Interdisciplinario de Neurociencias de Valparaíso, Universidad de Valparaíso, Valparaíso, ChileDepartamento de Fisiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, ChileInstitut Curie, PSL Research University, CNRS, UMR 144, Paris, FranceInstitut Pierre-Gilles de Gennes, PSL Research University, Paris, FranceFacultad de Ciencias, Instituto de Neurociencias and Centro Interdisciplinario de Neurociencias de Valparaíso, Universidad de Valparaíso, Valparaíso, ChileFacultad de Ciencias, Instituto de Neurociencias and Centro Interdisciplinario de Neurociencias de Valparaíso, Universidad de Valparaíso, Valparaíso, ChileFacultad de Ciencias, Instituto de Neurociencias and Centro Interdisciplinario de Neurociencias de Valparaíso, Universidad de Valparaíso, Valparaíso, ChileDepartamento de Fisiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, ChileFacultad de Ciencias, Instituto de Neurociencias and Centro Interdisciplinario de Neurociencias de Valparaíso, Universidad de Valparaíso, Valparaíso, ChileMast cells (MCs) release pro-inflammatory mediators through a process called degranulation response. The latter may be induced by several conditions, including antigen recognition through immunoglobulin E (IgE) or “cross-linking,” classically associated with Type I hypersensitivity reactions. Early in this reaction, Ca2+ influx and subsequent increase of intracellular free Ca2+ concentration are essential for MC degranulation. Several membrane channels that mediate Ca2+ influx have been proposed, but their role remains elusive. Here, we evaluated the possible contribution of pannexin-1 channels (Panx1 Chs), well-known as ATP-releasing channels, in the increase of intracellular Ca2+ triggered during cross-linking reaction of MCs. The contribution of Panx1 Chs in the degranulation response was evaluated in MCs from wild type (WT) and Panx1 knock out (Panx1−/−) mice after anti-ovalbumin (OVA) IgE sensitization. Notably, the degranulation response (toluidine blue and histamine release) was absent in Panx1−/− MCs. Moreover, WT MCs showed a rapid and transient increase in Ca2+ signal followed by a sustained increase after antigen stimulation. However, the sustained increase in Ca2+ signal triggered by OVA was absent in Panx1−/− MCs. Furthermore, OVA stimulation increased the membrane permeability assessed by dye uptake, a prevented response by Panx1 Ch but not by connexin hemichannel blockers and without effect on Panx1−/− MCs. Interestingly, the increase in membrane permeability of WT MCs was also prevented by suramin, a P2 purinergic inhibitor, suggesting that Panx1 Chs act as ATP-releasing channels impermeable to Ca2+. Accordingly, stimulation with exogenous ATP restored the degranulation response and sustained increase in Ca2+ signal of OVA stimulated Panx1−/− MCs. Moreover, opening of Panx1 Chs in Panx1 transfected HeLa cells increased dye uptake and ATP release but did not promote Ca2+ influx, confirming that Panx1 Chs permeable to ATP are not permeable to Ca2+. These data strongly suggest that during antigen recognition, Panx1 Chs contribute to the sustained Ca2+ signal increase via release of ATP that activates P2 receptors, playing a critical role in the sequential events that leads to degranulation response during Type I hypersensitivity reactions.https://www.frontiersin.org/article/10.3389/fimmu.2019.02703/fullinflammationimmune cellsovalbuminpannexondegranulationhistamine |