Research article - Peer-reviewed, 2020
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Mast cell chymase protects against acute ischemic kidney injury by limiting neutrophil hyperactivation and recruitment
Madjene, Lydia Celia; Danelli, Luca; Dahdah, Albert; Vibhushan, Shamila; Bex-Coudrat, Julie; Pacreau, Emeline; Vaugier, Celine; Claver, Julien; Rolas, Loic; Pons, Maguelonne; Madera-Salcedo, Iris Karina; Beghdadi, Walid; El Ghoneimi, Alaa; Benhamou, Marc; Launay, Pierre; Abrink, Magnus; Pejler, Gunnar; Moura, Ivan Cruz; Charles, Nicolas; Daugas, Eric;Show more authors
Abstract
Here we investigated the role of murine mast cell protease 4 (MCPT4), the functional counterpart of human mast cell chymase, in an experimental model of renal ischemia reperfusion injury, a major cause of acute kidney injury. MCPT4-deficient mice had worsened kidney function compared to wildtype mice. MCPT4 absence exacerbated pathologic neutrophil infiltration in the kidney and increased kidney myeloperoxidase expression, cell death and necrosis. In kidneys with ischemia reperfusion injury, when compared to wildtype mice, MCPT4-deficient mice showed increased surface expression of adhesion molecules necessary for leukocyte extravasation including neutrophil CD162 and endothelial cell CD54. In vitro, human chymase mediated the cleavage of neutrophil expressed CD162 and also CD54, P- and E-Selectin expressed on human glomerular endothelial cells. MCPT4 also dampened systemic neutrophil activation after renal ischemia reperfusion injury as neutrophils expressed more CD11b integrin and produced more reactive oxygen species in MCPT4-deficient mice. Accordingly, after renal injury, neutrophil migration to an inflammatory site distal from the kidney was increased in MCPT4-deficient versus wildtype mice. Thus, contrary to the described overall aggravating role of mast cells, one granule-released mediator, the MCPT4 chymase, exhibits a potent anti-inflammatory function in renal ischemia reperfusion injury by controlling neutrophil extravasation and activation thereby limiting associated damage.Keywords
acute kidney injury; acute rejection; inflammation; ischemia reperfusionPublished in
Kidney International2020, volume: 97, number: 3, pages: 516-527
Publisher: ELSEVIER SCIENCE INC
Authors' information
Madjene, Lydia Celia
CNRS
Danelli, Luca
Francis Crick Inst
Dahdah, Albert
INSERM
Vibhushan, Shamila
INSERM
Bex-Coudrat, Julie
Univ Paris Diderot
Pacreau, Emeline
Univ Paris Diderot
Vaugier, Celine
Paris Descartes Sorbonne Paris Cite Univ
Claver, Julien
Univ Paris Diderot
Rolas, Loic
INSERM
Pons, Maguelonne
Univ Paris Diderot
Madera-Salcedo, Iris Karina
Inst Nacl Ciencias Med and Nutr Salvador Zubiran
Beghdadi, Walid
INSERM
El Ghoneimi, Alaa
INSERM
Benhamou, Marc
CNRS
Launay, Pierre
Univ Paris Diderot
Swedish University of Agricultural Sciences, Department of Biomedical Science and Veterinary Public Health
Swedish University of Agricultural Sciences, Department of Anatomy, Physiology and Biochemistry (AFB)
Uppsala University
Moura, Ivan Cruz
Paris Descartes Sorbonne Paris Cite Univ
Charles, Nicolas
INSERM
UKÄ Subject classification
Immunology in the medical area
Publication Identifiers
DOI: https://doi.org/10.1016/j.kint.2019.08.037
URI (permanent link to this page)
https://res.slu.se/id/publ/104823