title: Specific expression of heme oxygenase-1 by myeloid cells modulates renal ischemia-reperfusion injury.
abstract: Renal ischemia-reperfusion injury (IRI) is a major risk factor for delayed graft function in renal transplantation. Compelling evidence exists that the stress-responsive enzyme, heme oxygenase-1 (HO-1) mediates protection against IRI. However, the role of myeloid HO-1 during IRI remains poorly characterized. Mice with myeloid-restricted deletion of HO-1 (HO-1M-KO), littermate (LT), and wild-type (WT) mice were subjected to renal IRI or sham procedures and sacrificed after 24 hours or 7 days. In comparison to LT, HO-1M-KOexhibited significant renal histological damage, pro-inflammatory responses and oxidative stress 24 hours after reperfusion. HO-1M-KOmice also displayed impaired tubular repair and increased renal fibrosis 7 days after IRI. In WT mice, HO-1 induction with hemin specifically upregulated HO-1 within the CD11b+F4/80losubset of the renal myeloid cells. Prior administration of hemin to renal IRI was associated with significant increase of the renal HO-1+CD11b+F4/80lomyeloid cells in comparison to control mice. In contrast, this hemin-mediated protection was abolished in HO-1M-KOmice. In conclusion, myeloid HO-1 appears as a critical protective pathway against renal IRI and could be an interesting therapeutic target in renal transplantation.
authors.affiliation: Institute for Medical Immunology (IMI), Université Libre de Bruxelles, Gosselies, Belgium. mrossi@ulb.ac.be.|Department of Urology, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium. mrossi@ulb.ac.be.
authors.forename: Maxime
authors.initials: M
authors.lastname: Rossi
authors.affiliation: Institute for Medical Immunology (IMI), Université Libre de Bruxelles, Gosselies, Belgium.|Department of Nephrology, Dialysis and Renal Transplantation, CHU de Poitiers, Poitiers, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Thierry
authors.affiliation: Institute for Medical Immunology (IMI), Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Delbauve
authors.affiliation: Laboratory of Immunobiology, Institute for Molecular Biology and Medicine, Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Preyat
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: Miguel P
authors.identifier: 0000-0002-9314-4833
authors.initials: MP
authors.lastname: Soares
authors.affiliation: Department of Urology, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Thierry
authors.initials: T
authors.lastname: Roumeguère
authors.affiliation: Institute for Medical Immunology (IMI), Université Libre de Bruxelles, Gosselies, Belgium.|Laboratory of Immunobiology, Institute for Molecular Biology and Medicine, Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: Oberdan
authors.initials: O
authors.lastname: Leo
authors.affiliation: Institute for Medical Immunology (IMI), Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: Véronique
authors.initials: V
authors.lastname: Flamand
authors.affiliation: Institute for Medical Immunology (IMI), Université Libre de Bruxelles, Gosselies, Belgium.|Department of Nephrology, Dialysis and Renal Transplantation, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Alain
authors.initials: A
authors.lastname: Le Moine
authors.affiliation: Institute for Medical Immunology (IMI), Université Libre de Bruxelles, Gosselies, Belgium. Jean-Michel.Hougardy@erasme.ulb.ac.be.|Department of Nephrology, Dialysis and Renal Transplantation, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium. Jean-Michel.Hougardy@erasme.ulb.ac.be.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Hougardy
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D055786:Gene Knockout Techniques; D051547:Heme Oxygenase-1 / Q000235:genetics* / Q000378:metabolism; D006427:Hemin / Q000494:pharmacology; D007674:Kidney Diseases / Q000209:etiology* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress; D015427:Reperfusion Injury / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D008565:Membrane Proteins; D006427:Hemin; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse