Analysis of Mrgprb2 Receptor-Evoked Ca2+ Signaling in Bone Marrow Derived (BMMC) and Peritoneal (PMC) Mast Cells of TRPC-Deficient Mice

Mast cells are a heterogeneous group of immune cells. The simplest and commonly accepted classification divides them in two groups according to their protease content. We have compared the action of diverse secretagogues on bone marrow derived (BMMC) and peritoneal (PMC) mast cells which represent c...

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Autores: Tsvilovskyy, Volodymyr, Solis Lopez, Alejandra, Almering, Julia, Richter, Christin, Birnbaumer, Lutz, Dietrich, Alexander, Freichel, Marc
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:Argentina
Recursos:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/141818
Acesso em linha:http://hdl.handle.net/11336/141818
Access Level:acceso abierto
Palavra-chave:CONNECTIVE TISSUE TYPE MAST CELLS
INTRACELLULAR CALCIUM
MAST CELLS DEGRANULATION
MRGPRB2 RECEPTOR
MUCOSAL TISSUE TYPE MAST CELLS
SECRETAGOGUES
TRPC CHANNELS
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
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oai_identifier_str oai:ri.conicet.gov.ar:11336/141818
network_acronym_str AR
network_name_str Argentina
repository_id_str
dc.title.none.fl_str_mv Analysis of Mrgprb2 Receptor-Evoked Ca2+ Signaling in Bone Marrow Derived (BMMC) and Peritoneal (PMC) Mast Cells of TRPC-Deficient Mice
title Analysis of Mrgprb2 Receptor-Evoked Ca2+ Signaling in Bone Marrow Derived (BMMC) and Peritoneal (PMC) Mast Cells of TRPC-Deficient Mice
spellingShingle Analysis of Mrgprb2 Receptor-Evoked Ca2+ Signaling in Bone Marrow Derived (BMMC) and Peritoneal (PMC) Mast Cells of TRPC-Deficient Mice
Tsvilovskyy, Volodymyr
CONNECTIVE TISSUE TYPE MAST CELLS
INTRACELLULAR CALCIUM
MAST CELLS DEGRANULATION
MRGPRB2 RECEPTOR
MUCOSAL TISSUE TYPE MAST CELLS
SECRETAGOGUES
TRPC CHANNELS
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
title_short Analysis of Mrgprb2 Receptor-Evoked Ca2+ Signaling in Bone Marrow Derived (BMMC) and Peritoneal (PMC) Mast Cells of TRPC-Deficient Mice
title_full Analysis of Mrgprb2 Receptor-Evoked Ca2+ Signaling in Bone Marrow Derived (BMMC) and Peritoneal (PMC) Mast Cells of TRPC-Deficient Mice
title_fullStr Analysis of Mrgprb2 Receptor-Evoked Ca2+ Signaling in Bone Marrow Derived (BMMC) and Peritoneal (PMC) Mast Cells of TRPC-Deficient Mice
title_full_unstemmed Analysis of Mrgprb2 Receptor-Evoked Ca2+ Signaling in Bone Marrow Derived (BMMC) and Peritoneal (PMC) Mast Cells of TRPC-Deficient Mice
title_sort Analysis of Mrgprb2 Receptor-Evoked Ca2+ Signaling in Bone Marrow Derived (BMMC) and Peritoneal (PMC) Mast Cells of TRPC-Deficient Mice
dc.creator.none.fl_str_mv Tsvilovskyy, Volodymyr
Solis Lopez, Alejandra
Almering, Julia
Richter, Christin
Birnbaumer, Lutz
Dietrich, Alexander
Freichel, Marc
author Tsvilovskyy, Volodymyr
author_facet Tsvilovskyy, Volodymyr
Solis Lopez, Alejandra
Almering, Julia
Richter, Christin
Birnbaumer, Lutz
Dietrich, Alexander
Freichel, Marc
author_role author
author2 Solis Lopez, Alejandra
Almering, Julia
Richter, Christin
Birnbaumer, Lutz
Dietrich, Alexander
Freichel, Marc
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv CONNECTIVE TISSUE TYPE MAST CELLS
INTRACELLULAR CALCIUM
MAST CELLS DEGRANULATION
MRGPRB2 RECEPTOR
MUCOSAL TISSUE TYPE MAST CELLS
SECRETAGOGUES
TRPC CHANNELS
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
topic CONNECTIVE TISSUE TYPE MAST CELLS
INTRACELLULAR CALCIUM
MAST CELLS DEGRANULATION
MRGPRB2 RECEPTOR
MUCOSAL TISSUE TYPE MAST CELLS
SECRETAGOGUES
TRPC CHANNELS
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
description Mast cells are a heterogeneous group of immune cells. The simplest and commonly accepted classification divides them in two groups according to their protease content. We have compared the action of diverse secretagogues on bone marrow derived (BMMC) and peritoneal (PMC) mast cells which represent classical models of mucosal and connective tissue type mast cells in mice. Whereas, antigen stimulation of the FcεRI receptors was similarly effective in triggering elevations of free intracellular Ca2+ concentration ([Ca2+]i) in both BMMC and PMC, robust [Ca2+]i rise following Endothelin-1 stimulation was observed only in a fraction of BMMC. Leukotriene C4 activating cysteinyl leukotriene type I receptors failed to evoke [Ca2+]i rise in either mast cell model. Stimulation of the recently identified target of many small-molecule drugs associated with systemic pseudo-allergic reactions, Mrgprb2, with compound 48/80, a mast cell activator with unknown receptor studied for many years, triggered Ca2+ oscillations in BMMC and robust [Ca2+]i rise in PMCs similarly to that evoked by FcεRI stimulation. [Ca2+]i rise in PMC could also be evoked by other Mrgprb2 agonists such as Tubocurarine, LL-37, and Substance P. The extent of [Ca2+]i rise correlated with mast cell degranulation. Expression analysis of TRPC channels as potential candidates mediating agonist evoked Ca2+ entry revealed the presence of transcripts of all members of the TRPC subfamily of TRP channels in PMCs. The amplitude and AUC of compound 48/80-evoked [Ca2+]i rise was reduced by ~20% in PMC from Trpc1/4/6−/− mice compared to Trpc1/4−/− littermatched control mice, whereas FcεRI-evoked [Ca2+]i rise was unaltered. Whole-cell patch clamp recordings showed that the reduction in compound 48/80-evoked [Ca2+]i rise in Trpc1/4/6−/− PMC was accompanied by a reduced amplitude of Compound 48/80-induced cation currents which exhibited typical features of TRPC currents. Together, this study demonstrates that PMC are an appropriate mast cell model to study mechanisms of Mrgprb2 receptor-mediated mast cell activation, and it reveals that TRPC channels contribute at least partially to Mrgprb2-mediated mast cellactivation but not following FcεRI stimulation. However, the channels conducting most of the Ca2+ entry in mast cells triggered by Mrgprb2 receptor stimulation remains to be identified.
publishDate 2020
dc.date.none.fl_str_mv 2020-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/141818
Tsvilovskyy, Volodymyr; Solis Lopez, Alejandra; Almering, Julia; Richter, Christin; Birnbaumer, Lutz; et al.; Analysis of Mrgprb2 Receptor-Evoked Ca2+ Signaling in Bone Marrow Derived (BMMC) and Peritoneal (PMC) Mast Cells of TRPC-Deficient Mice; Frontiers Media; Frontiers in Immunology; 11; 4-2020; 1-15
1664-3224
1664-3224
CONICET Digital
CONICET
url http://hdl.handle.net/11336/141818
identifier_str_mv Tsvilovskyy, Volodymyr; Solis Lopez, Alejandra; Almering, Julia; Richter, Christin; Birnbaumer, Lutz; et al.; Analysis of Mrgprb2 Receptor-Evoked Ca2+ Signaling in Bone Marrow Derived (BMMC) and Peritoneal (PMC) Mast Cells of TRPC-Deficient Mice; Frontiers Media; Frontiers in Immunology; 11; 4-2020; 1-15
1664-3224
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fimmu.2020.00564/full
info:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2020.00564
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1799195489359364096
spelling Analysis of Mrgprb2 Receptor-Evoked Ca2+ Signaling in Bone Marrow Derived (BMMC) and Peritoneal (PMC) Mast Cells of TRPC-Deficient MiceTsvilovskyy, VolodymyrSolis Lopez, AlejandraAlmering, JuliaRichter, ChristinBirnbaumer, LutzDietrich, AlexanderFreichel, MarcCONNECTIVE TISSUE TYPE MAST CELLSINTRACELLULAR CALCIUMMAST CELLS DEGRANULATIONMRGPRB2 RECEPTORMUCOSAL TISSUE TYPE MAST CELLSSECRETAGOGUESTRPC CHANNELShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Mast cells are a heterogeneous group of immune cells. The simplest and commonly accepted classification divides them in two groups according to their protease content. We have compared the action of diverse secretagogues on bone marrow derived (BMMC) and peritoneal (PMC) mast cells which represent classical models of mucosal and connective tissue type mast cells in mice. Whereas, antigen stimulation of the FcεRI receptors was similarly effective in triggering elevations of free intracellular Ca2+ concentration ([Ca2+]i) in both BMMC and PMC, robust [Ca2+]i rise following Endothelin-1 stimulation was observed only in a fraction of BMMC. Leukotriene C4 activating cysteinyl leukotriene type I receptors failed to evoke [Ca2+]i rise in either mast cell model. Stimulation of the recently identified target of many small-molecule drugs associated with systemic pseudo-allergic reactions, Mrgprb2, with compound 48/80, a mast cell activator with unknown receptor studied for many years, triggered Ca2+ oscillations in BMMC and robust [Ca2+]i rise in PMCs similarly to that evoked by FcεRI stimulation. [Ca2+]i rise in PMC could also be evoked by other Mrgprb2 agonists such as Tubocurarine, LL-37, and Substance P. The extent of [Ca2+]i rise correlated with mast cell degranulation. Expression analysis of TRPC channels as potential candidates mediating agonist evoked Ca2+ entry revealed the presence of transcripts of all members of the TRPC subfamily of TRP channels in PMCs. The amplitude and AUC of compound 48/80-evoked [Ca2+]i rise was reduced by ~20% in PMC from Trpc1/4/6−/− mice compared to Trpc1/4−/− littermatched control mice, whereas FcεRI-evoked [Ca2+]i rise was unaltered. Whole-cell patch clamp recordings showed that the reduction in compound 48/80-evoked [Ca2+]i rise in Trpc1/4/6−/− PMC was accompanied by a reduced amplitude of Compound 48/80-induced cation currents which exhibited typical features of TRPC currents. Together, this study demonstrates that PMC are an appropriate mast cell model to study mechanisms of Mrgprb2 receptor-mediated mast cell activation, and it reveals that TRPC channels contribute at least partially to Mrgprb2-mediated mast cellactivation but not following FcεRI stimulation. However, the channels conducting most of the Ca2+ entry in mast cells triggered by Mrgprb2 receptor stimulation remains to be identified.Fil: Tsvilovskyy, Volodymyr. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Solis Lopez, Alejandra. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Almering, Julia. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Richter, Christin. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Dietrich, Alexander. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Freichel, Marc. Ruprecht Karls Universitat Heidelberg; AlemaniaFrontiers Media2020-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/141818Tsvilovskyy, Volodymyr; Solis Lopez, Alejandra; Almering, Julia; Richter, Christin; Birnbaumer, Lutz; et al.; Analysis of Mrgprb2 Receptor-Evoked Ca2+ Signaling in Bone Marrow Derived (BMMC) and Peritoneal (PMC) Mast Cells of TRPC-Deficient Mice; Frontiers Media; Frontiers in Immunology; 11; 4-2020; 1-151664-32241664-3224CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fimmu.2020.00564/fullinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2020.00564info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2024-05-08T13:54:04Zoai:ri.conicet.gov.ar:11336/141818instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982024-05-08 13:54:04.499CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
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