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Forskningsartikel2020Vetenskapligt granskadÖppen tillgång

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;
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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.


acute kidney injury; acute rejection; inflammation; ischemia reperfusion

Publicerad i

Kidney International
2020, Volym: 97, nummer: 3, sidor: 516-527