Rossi, MaximeThierry, AntoineDelbauve, SandrinePreyat, NicolasSoares, Miguel P.Roumeguère, ThierryLeo, OberdanFlamand, VéroniqueLe Moine, AlainHougardy, Jean-Michel2017-03-172017-03-172017-03-15Scientific Reports 7, Article number: 197 (2017) doi:10.1038/s41598-017-00220-whttp://hdl.handle.net/10400.7/739This work was presented in abstract form at the 17th Congress of the European Society for Organ Transplantation (ESOT) in Brussels, Belgium (Brief Oral Presentation, BOS04 – Ischemia, Reperfusion, Metabolism and Aging, abstract N°BO33; 13–16 September 2015) and at the 16th Congress of the European Association of Urology (EAU) in Munich, Germany (Poster Session 48, Kidney Transplant: From Bench to clinical practice, abstract n°603; 11–15 March 2016).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-1(M-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-1(M-KO) exhibited significant renal histological damage, pro-inflammatory responses and oxidative stress 24 hours after reperfusion. HO-1(M-KO) mice 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(+) F4/80(lo) subset of the renal myeloid cells. Prior administration of hemin to renal IRI was associated with significant increase of the renal HO-1(+) CD11b(+) F4/80(lo) myeloid cells in comparison to control mice. In contrast, this hemin-mediated protection was abolished in HO-1(M-KO) mice. In conclusion, myeloid HO-1 appears as a critical protective pathway against renal IRI and could be an interesting therapeutic target in renal transplantation.engAcute kidney injuryMonocytes and macrophagesTranslational immunologyjournal article10.1038/s41598-017-00220-w