title: Heme Oxygenase-1 Regulates Myeloid Cell Trafficking in AKI.
abstract: Renal ischemia-reperfusion injury is mediated by a complex cascade of events, including the immune response, that occur secondary to injury to renal epithelial cells. We tested the hypothesis that heme oxygenase-1 (HO-1) expression, which is protective in ischemia-reperfusion injury, regulates trafficking of myeloid-derived immune cells in the kidney. Age-matched male wild-type (HO-1(+/+)), HO-1-knockout (HO-1(-/-)), and humanized HO-1-overexpressing (HBAC) mice underwent bilateral renal ischemia for 10 minutes. Ischemia-reperfusion injury resulted in significantly worse renal structure and function and increased mortality in HO-1(-/-) mice. In addition, there were more macrophages (CD45(+) CD11b(hi)F4/80(lo)) and neutrophils (CD45(+) CD11b(hi) MHCII(-) Gr-1(hi)) in HO-1(-/-) kidneys than in sham and HO-1(+/+) control kidneys subjected to ischemia-reperfusion. However, ischemic injury resulted in a significant decrease in the intrarenal resident dendritic cell (DC; CD45(+)MHCII(+)CD11b(lo)F4/80(hi)) population in HO-1(-/-) kidneys compared with controls. Syngeneic transplant experiments utilizing green fluorescent protein-positive HO-1(+/+) or HO-1(-/-) donor kidneys and green fluorescent protein-negative HO-1(+/+) recipients confirmed increased migration of the resident DC population from HO-1(-/-) donor kidneys, compared to HO-1(+/+) donor kidneys, to the peripheral lymphoid organs. This effect on renal DC migration was corroborated in myeloid-specific HO-1(-/-) mice subjected to bilateral ischemia. These mice also displayed impaired renal recovery and increased fibrosis at day 7 after injury. These results highlight an important role for HO-1 in orchestrating the trafficking of myeloid cells in AKI, which may represent a key pathway for therapeutic intervention.
authors: Nephrology Research and Training Center, Division of Cardiothoracic Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama; and.
authors: Travis D
authors: TD
authors: Hull
authors: Nephrology Research and Training Center.
authors: Ahmed I
authors: AI
authors: Kamal
authors: Nephrology Research and Training Center.
authors: Ravindra
authors: R
authors: Boddu
authors: Nephrology Research and Training Center.
authors: Subhashini
authors: S
authors: Bolisetty
authors: Nephrology Research and Training Center, Division of Cardiothoracic Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama; and.
authors: Lingling
authors: L
authors: Guo
authors: Nephrology Research and Training Center.
authors: Cornelia C
authors: CC
authors: Tisher
authors: Nephrology Research and Training Center.
authors: Sunil
authors: S
authors: Rangarajan
authors: Nephrology Research and Training Center, Division of Nephrology, Department of Medicine, and.
authors: Bo
authors: B
authors: Chen
authors: Nephrology Research and Training Center, Birmingham Veterans Administration Medical Center, Birmingham, Alabama.
authors: Lisa M
authors: LM
authors: Curtis
authors: Nephrology Research and Training Center, Division of Cardiothoracic Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama; and agarwal@uab.edu jgeorge@uab.edu.
authors: James F
authors: JF
authors: George
authors: Nephrology Research and Training Center, Birmingham Veterans Administration Medical Center, Birmingham, Alabama agarwal@uab.edu jgeorge@uab.edu.
authors: Anupam
authors: A
authors: Agarwal
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D003713:Dendritic Cells; D005355:Fibrosis; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000502:physiology*; D007113:Immunity, Innate; D015850:Interleukin-6 / Q000378:metabolism; D007511:Ischemia / Q000209:etiology; D007668:Kidney / Q000098:blood supply / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D008264:Macrophages; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000378:metabolism; D009504:Neutrophils; D015427:Reperfusion Injury / Q000150:complications; D013154:Spleen / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D051547:Heme Oxygenase-1
keywords: ARF; heme oxygenase; macrophages