Early Phase Mast Cell Activation Determines the Chronic Outcome of Renal Ischemia-Reperfusion Injury.
Ischemia-reperfusion injury (IRI) is an important cause of acute kidney injury that can lead to end-stage renal failure. Although the ensuing inflammatory response can restore homeostasis, a consecutive maladaptive repair and persistent inflammation represent important risk factors for postischemic chronic kidney disease development. In this study, we investigated the role of mast cells in both the early and late phases of the inflammatory response in experimental models of acute and chronic renal IRI using our recently developed mouse model that allows conditional ablation of mast cells. Depletion of mast cells prior to IRI resulted in improved renal function due to diminished local inflammatory cytokine/chemokine levels and neutrophil recruitment to the kidneys after the acute injury phase (48 h post-IRI). Furthermore, although not completely protected, mast cell-depleted mice displayed less organ atrophy and fibrosis than did wild-type mice during the chronic phases (2 and 6 wk post-IRI) of disease development. Conversely, mast cell ablation after the acute phase of IRI had no impact on organ atrophy, tubular necrosis, or fibrosis. Thus, our results suggest a deleterious role of mast cells during the acute inflammatory phase of IRI promoting subsequent fibrosis development, but not during the chronic phase of the disease.
INSERM U1149, Centre de Recherche sur l'Inflammation, 75018 Paris, France.|CNRS ERL8252, 75018 Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Faculté de Médecine, Site Xavier Bichat, Laboratoire d' Excellence Inflamex, 75018 Paris, France; and.
Luca
0000-0003-1222-0732
L
Danelli
INSERM U1149, Centre de Recherche sur l'Inflammation, 75018 Paris, France.|CNRS ERL8252, 75018 Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Faculté de Médecine, Site Xavier Bichat, Laboratoire d' Excellence Inflamex, 75018 Paris, France; and.
Lydia Celia
0000-0003-4156-8041
LC
Madjene
INSERM U1149, Centre de Recherche sur l'Inflammation, 75018 Paris, France.|CNRS ERL8252, 75018 Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Faculté de Médecine, Site Xavier Bichat, Laboratoire d' Excellence Inflamex, 75018 Paris, France; and.
Iris
0000-0002-0741-9248
I
Madera-Salcedo
INSERM U1149, Centre de Recherche sur l'Inflammation, 75018 Paris, France.|CNRS ERL8252, 75018 Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Faculté de Médecine, Site Xavier Bichat, Laboratoire d' Excellence Inflamex, 75018 Paris, France; and.
Gregory
0000-0003-4887-5095
G
Gautier
INSERM U1149, Centre de Recherche sur l'Inflammation, 75018 Paris, France.|CNRS ERL8252, 75018 Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Faculté de Médecine, Site Xavier Bichat, Laboratoire d' Excellence Inflamex, 75018 Paris, France; and.
Emeline
0000-0001-6289-3869
E
Pacreau
INSERM U1149, Centre de Recherche sur l'Inflammation, 75018 Paris, France.|CNRS ERL8252, 75018 Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Faculté de Médecine, Site Xavier Bichat, Laboratoire d' Excellence Inflamex, 75018 Paris, France; and.
Sanae
0000-0001-7919-2233
S
Ben Mkaddem
INSERM U1149, Centre de Recherche sur l'Inflammation, 75018 Paris, France.|CNRS ERL8252, 75018 Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Faculté de Médecine, Site Xavier Bichat, Laboratoire d' Excellence Inflamex, 75018 Paris, France; and.
Nicolas
N
Charles
INSERM U1149, Centre de Recherche sur l'Inflammation, 75018 Paris, France.|CNRS ERL8252, 75018 Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Faculté de Médecine, Site Xavier Bichat, Laboratoire d' Excellence Inflamex, 75018 Paris, France; and.|Service de Néphrologie, Départements-Hospitalo-Universitaires FIRE, Hôpital Bichat-Claude Bernard, Assistance Publique de Paris, 75018 Paris, France.
Eric
E
Daugas
INSERM U1149, Centre de Recherche sur l'Inflammation, 75018 Paris, France.|CNRS ERL8252, 75018 Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Faculté de Médecine, Site Xavier Bichat, Laboratoire d' Excellence Inflamex, 75018 Paris, France; and.
Pierre
P
Launay
INSERM U1149, Centre de Recherche sur l'Inflammation, 75018 Paris, France; ulrich.blank@inserm.fr.|CNRS ERL8252, 75018 Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Faculté de Médecine, Site Xavier Bichat, Laboratoire d' Excellence Inflamex, 75018 Paris, France; and.
Ulrich
0000-0002-2661-2983
U
Blank
D058186:Acute Kidney Injury / Q000276:immunology*; D000818:Animals; D015550:Cell Degranulation; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005355:Fibrosis; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007668:Kidney / Q000276:immunology* / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D020556:Neutrophil Infiltration; D017455:Receptors, IgE / Q000235:genetics; D015427:Reperfusion Injury / Q000276:immunology*
D016207:Cytokines; D018836:Inflammation Mediators; C502447:MS4A2 protein, human; D017455:Receptors, IgE