Analysis of mrgprb2 receptor-evoked Ca 2+ signaling in bone marrow derived (BMMC) and peritoneal (PMC) mast cells of TRPC-deficient mice

Abstract: 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 r...

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Detalles Bibliográficos
Autores principales: Tsvilovskyy, Volodymyr, Solis-López, Alejandra, Almering, Julia, Richter, Christin, Birnbaumer, Lutz, Dietrich, Alexander, Freichel, Marc
Formato: Artículo
Lenguaje:Inglés
Publicado: Frontiers Media 2022
Materias:
CANALES IONICOS
CALCIO
MASTOCITOS
PERITONEO
MEDULA OSEA
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/14247
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139-123456789-14247
record_format dspace
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic CANALES IONICOS
CALCIO
MASTOCITOS
PERITONEO
MEDULA OSEA
spellingShingle CANALES IONICOS
CALCIO
MASTOCITOS
PERITONEO
MEDULA OSEA
Tsvilovskyy, Volodymyr
Solis-López, Alejandra
Almering, Julia
Richter, Christin
Birnbaumer, Lutz
Dietrich, Alexander
Freichel, Marc
Analysis of mrgprb2 receptor-evoked Ca 2+ signaling in bone marrow derived (BMMC) and peritoneal (PMC) mast cells of TRPC-deficient mice
topic_facet CANALES IONICOS
CALCIO
MASTOCITOS
PERITONEO
MEDULA OSEA
description Abstract: 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.
format Artículo
author Tsvilovskyy, Volodymyr
Solis-López, Alejandra
Almering, Julia
Richter, Christin
Birnbaumer, Lutz
Dietrich, Alexander
Freichel, Marc
author_facet Tsvilovskyy, Volodymyr
Solis-López, Alejandra
Almering, Julia
Richter, Christin
Birnbaumer, Lutz
Dietrich, Alexander
Freichel, Marc
author_sort Tsvilovskyy, Volodymyr
title Analysis of mrgprb2 receptor-evoked Ca 2+ signaling in bone marrow derived (BMMC) and peritoneal (PMC) mast cells of TRPC-deficient mice
title_short Analysis of mrgprb2 receptor-evoked Ca 2+ signaling in bone marrow derived (BMMC) and peritoneal (PMC) mast cells of TRPC-deficient mice
title_full Analysis of mrgprb2 receptor-evoked Ca 2+ signaling in bone marrow derived (BMMC) and peritoneal (PMC) mast cells of TRPC-deficient mice
title_fullStr Analysis of mrgprb2 receptor-evoked Ca 2+ signaling in bone marrow derived (BMMC) and peritoneal (PMC) mast cells of TRPC-deficient mice
title_full_unstemmed Analysis of mrgprb2 receptor-evoked Ca 2+ signaling in bone marrow derived (BMMC) and peritoneal (PMC) mast cells of TRPC-deficient mice
title_sort analysis of mrgprb2 receptor-evoked ca 2+ signaling in bone marrow derived (bmmc) and peritoneal (pmc) mast cells of trpc-deficient mice
publisher Frontiers Media
publishDate 2022
url https://repositorio.uca.edu.ar/handle/123456789/14247
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