Frontiers in Immunology (Nov 2018)
Mast Cell Degranulation Exacerbates Skin Rejection by Enhancing Neutrophil Recruitment
- 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
Affiliations
- Flavie Ngo Nyekel
- INSERM UMRS 1149, Paris, France
- Flavie Ngo Nyekel
- CNRS ERL8252, Paris, France
- Flavie Ngo Nyekel
- Université Paris Diderot, Sorbonne Paris Cité, Laboratoire D'excellence INFLAMEX, Paris, France
- Emeline Pacreau
- INSERM UMRS 1149, Paris, France
- Emeline Pacreau
- CNRS ERL8252, Paris, France
- Emeline Pacreau
- Université Paris Diderot, Sorbonne Paris Cité, Laboratoire D'excellence INFLAMEX, Paris, France
- Samira Benadda
- INSERM UMRS 1149, Paris, France
- Samira Benadda
- Université Paris Diderot, Sorbonne Paris Cité, Laboratoire D'excellence INFLAMEX, Paris, France
- Rasha Msallam
- Institut Necker Enfants Malades, INSERM U1151, CNRS, UMR8253, Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
- Rasha Msallam
- Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
- Magnus Åbrink
- Section of Immunology, Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, VHC, Uppsala, Sweden
- Gunnar Pejler
- Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden
- Gunnar Pejler
- Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
- Jean Davoust
- Institut Necker Enfants Malades, INSERM U1151, CNRS, UMR8253, Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
- Marc Benhamou
- INSERM UMRS 1149, Paris, France
- Marc Benhamou
- CNRS ERL8252, Paris, France
- Marc Benhamou
- Université Paris Diderot, Sorbonne Paris Cité, Laboratoire D'excellence INFLAMEX, Paris, France
- Nicolas Charles
- INSERM UMRS 1149, Paris, France
- Nicolas Charles
- CNRS ERL8252, Paris, France
- Nicolas Charles
- Université Paris Diderot, Sorbonne Paris Cité, Laboratoire D'excellence INFLAMEX, Paris, France
- Pierre Launay
- INSERM UMRS 1149, Paris, France
- Pierre Launay
- CNRS ERL8252, Paris, France
- Pierre Launay
- Université Paris Diderot, Sorbonne Paris Cité, Laboratoire D'excellence INFLAMEX, Paris, France
- Ulrich Blank
- INSERM UMRS 1149, Paris, France
- Ulrich Blank
- CNRS ERL8252, Paris, France
- Ulrich Blank
- Université Paris Diderot, Sorbonne Paris Cité, Laboratoire D'excellence INFLAMEX, Paris, France
- Gregory Gautier
- INSERM UMRS 1149, Paris, France
- Gregory Gautier
- CNRS ERL8252, Paris, France
- Gregory Gautier
- Université Paris Diderot, Sorbonne Paris Cité, Laboratoire D'excellence INFLAMEX, Paris, France
- DOI
- https://doi.org/10.3389/fimmu.2018.02690
- Journal volume & issue
-
Vol. 9
Abstract
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.
Keywords
