Mast Cell Degranulation Exacerbates Skin Rejection by Enhancing Neutrophil Recruitment

Recent evidences indicate an important role of tissue inflammatory responses by innate immune cells in allograft acceptance and survival. Here we investigated the role of mast cells (MC) in an acute male to female skin allograft rejection model using red MC and basophil (RMB) mice enabling condition...

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Main Authors:	Flavie Ngo Nyekel, Emeline Pacreau, Samira Benadda, Rasha Msallam, Magnus Åbrink, Gunnar Pejler, Jean Davoust, Marc Benhamou, Nicolas Charles, Pierre Launay, Ulrich Blank, Gregory Gautier
Format:	Article
Language:	English
Published:	Frontiers Media S.A. 2018-11-01
Series:	Frontiers in Immunology
Subjects:	mast cells neutrophils degranulation skin transplantation
Online Access:	https://www.frontiersin.org/article/10.3389/fimmu.2018.02690/full

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spelling	doaj-19eba69396d14f69908173f038c7f8cf2020-11-24T21:46:38ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-11-01910.3389/fimmu.2018.02690415854Mast Cell Degranulation Exacerbates Skin Rejection by Enhancing Neutrophil RecruitmentFlavie Ngo Nyekel0Flavie Ngo Nyekel1Flavie Ngo Nyekel2Emeline Pacreau3Emeline Pacreau4Emeline Pacreau5Samira Benadda6Samira Benadda7Rasha Msallam8Rasha Msallam9Magnus Åbrink10Gunnar Pejler11Gunnar Pejler12Jean Davoust13Marc Benhamou14Marc Benhamou15Marc Benhamou16Nicolas Charles17Nicolas Charles18Nicolas Charles19Pierre Launay20Pierre Launay21Pierre Launay22Ulrich Blank23Ulrich Blank24Ulrich Blank25Gregory Gautier26Gregory Gautier27Gregory Gautier28INSERM UMRS 1149, Paris, FranceCNRS ERL8252, Paris, FranceUniversité Paris Diderot, Sorbonne Paris Cité, Laboratoire D'excellence INFLAMEX, Paris, FranceINSERM UMRS 1149, Paris, FranceCNRS ERL8252, Paris, FranceUniversité Paris Diderot, Sorbonne Paris Cité, Laboratoire D'excellence INFLAMEX, Paris, FranceINSERM UMRS 1149, Paris, FranceUniversité Paris Diderot, Sorbonne Paris Cité, Laboratoire D'excellence INFLAMEX, Paris, FranceInstitut Necker Enfants Malades, INSERM U1151, CNRS, UMR8253, Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, FranceSingapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore, SingaporeSection of Immunology, Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, VHC, Uppsala, SwedenDepartment of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, SwedenDepartment of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, SwedenInstitut Necker Enfants Malades, INSERM U1151, CNRS, UMR8253, Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, FranceINSERM UMRS 1149, Paris, FranceCNRS ERL8252, Paris, FranceUniversité Paris Diderot, Sorbonne Paris Cité, Laboratoire D'excellence INFLAMEX, Paris, FranceINSERM UMRS 1149, Paris, FranceCNRS ERL8252, Paris, FranceUniversité Paris Diderot, Sorbonne Paris Cité, Laboratoire D'excellence INFLAMEX, Paris, FranceINSERM UMRS 1149, Paris, FranceCNRS ERL8252, Paris, FranceUniversité Paris Diderot, Sorbonne Paris Cité, Laboratoire D'excellence INFLAMEX, Paris, FranceINSERM UMRS 1149, Paris, FranceCNRS ERL8252, Paris, FranceUniversité Paris Diderot, Sorbonne Paris Cité, Laboratoire D'excellence INFLAMEX, Paris, FranceINSERM UMRS 1149, Paris, FranceCNRS ERL8252, Paris, FranceUniversité Paris Diderot, Sorbonne Paris Cité, Laboratoire D'excellence INFLAMEX, Paris, FranceRecent evidences indicate an important role of tissue inflammatory responses by innate immune cells in allograft acceptance and survival. Here we investigated the role of mast cells (MC) in an acute male to female skin allograft rejection model using red MC and basophil (RMB) mice enabling conditional MC depletion. Kinetic analysis showed that MCs markedly accelerate skin rejection. They induced an early inflammatory response through degranulation and boosted local synthesis of KC, MIP-2, and TNF. This enhanced early neutrophil infiltration compared to a female-female graft-associated repair response. The uncontrolled neutrophil influx accelerated rejection as antibody-mediated depletion of neutrophils delayed skin rejection. Administration of cromolyn, a MC stabilizer and to a lesser extent ketotifen, a histamine type I receptor antagonist, and absence of MCPT4 chymase also delayed graft rejection. Together our data indicate that mediators contained in secretory granules of MC promote an inflammatory response with enhanced neutrophil infiltration that accelerate graft rejection.https://www.frontiersin.org/article/10.3389/fimmu.2018.02690/fullmast cellsneutrophilsdegranulationskintransplantation
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Flavie Ngo Nyekel Flavie Ngo Nyekel Flavie Ngo Nyekel Emeline Pacreau Emeline Pacreau Emeline Pacreau Samira Benadda Samira Benadda Rasha Msallam Rasha Msallam Magnus Åbrink Gunnar Pejler Gunnar Pejler Jean Davoust Marc Benhamou Marc Benhamou Marc Benhamou Nicolas Charles Nicolas Charles Nicolas Charles Pierre Launay Pierre Launay Pierre Launay Ulrich Blank Ulrich Blank Ulrich Blank Gregory Gautier Gregory Gautier Gregory Gautier
spellingShingle	Flavie Ngo Nyekel Flavie Ngo Nyekel Flavie Ngo Nyekel Emeline Pacreau Emeline Pacreau Emeline Pacreau Samira Benadda Samira Benadda Rasha Msallam Rasha Msallam Magnus Åbrink Gunnar Pejler Gunnar Pejler Jean Davoust Marc Benhamou Marc Benhamou Marc Benhamou Nicolas Charles Nicolas Charles Nicolas Charles Pierre Launay Pierre Launay Pierre Launay Ulrich Blank Ulrich Blank Ulrich Blank Gregory Gautier Gregory Gautier Gregory Gautier Mast Cell Degranulation Exacerbates Skin Rejection by Enhancing Neutrophil Recruitment Frontiers in Immunology mast cells neutrophils degranulation skin transplantation
author_facet	Flavie Ngo Nyekel Flavie Ngo Nyekel Flavie Ngo Nyekel Emeline Pacreau Emeline Pacreau Emeline Pacreau Samira Benadda Samira Benadda Rasha Msallam Rasha Msallam Magnus Åbrink Gunnar Pejler Gunnar Pejler Jean Davoust Marc Benhamou Marc Benhamou Marc Benhamou Nicolas Charles Nicolas Charles Nicolas Charles Pierre Launay Pierre Launay Pierre Launay Ulrich Blank Ulrich Blank Ulrich Blank Gregory Gautier Gregory Gautier Gregory Gautier
author_sort	Flavie Ngo Nyekel
title	Mast Cell Degranulation Exacerbates Skin Rejection by Enhancing Neutrophil Recruitment
title_short	Mast Cell Degranulation Exacerbates Skin Rejection by Enhancing Neutrophil Recruitment
title_full	Mast Cell Degranulation Exacerbates Skin Rejection by Enhancing Neutrophil Recruitment
title_fullStr	Mast Cell Degranulation Exacerbates Skin Rejection by Enhancing Neutrophil Recruitment
title_full_unstemmed	Mast Cell Degranulation Exacerbates Skin Rejection by Enhancing Neutrophil Recruitment
title_sort	mast cell degranulation exacerbates skin rejection by enhancing neutrophil recruitment
publisher	Frontiers Media S.A.
series	Frontiers in Immunology
issn	1664-3224
publishDate	2018-11-01
description	Recent evidences indicate an important role of tissue inflammatory responses by innate immune cells in allograft acceptance and survival. Here we investigated the role of mast cells (MC) in an acute male to female skin allograft rejection model using red MC and basophil (RMB) mice enabling conditional MC depletion. Kinetic analysis showed that MCs markedly accelerate skin rejection. They induced an early inflammatory response through degranulation and boosted local synthesis of KC, MIP-2, and TNF. This enhanced early neutrophil infiltration compared to a female-female graft-associated repair response. The uncontrolled neutrophil influx accelerated rejection as antibody-mediated depletion of neutrophils delayed skin rejection. Administration of cromolyn, a MC stabilizer and to a lesser extent ketotifen, a histamine type I receptor antagonist, and absence of MCPT4 chymase also delayed graft rejection. Together our data indicate that mediators contained in secretory granules of MC promote an inflammatory response with enhanced neutrophil infiltration that accelerate graft rejection.
topic	mast cells neutrophils degranulation skin transplantation
url	https://www.frontiersin.org/article/10.3389/fimmu.2018.02690/full
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Mast Cell Degranulation Exacerbates Skin Rejection by Enhancing Neutrophil Recruitment

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