Heme oxygenase-1 regulates myeloid cell trafficking in AKI

Academic Article


  • 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+ CD11bhiF4/80lo) and neutrophils (CD45+ CD11bhi MHCII2 Gr-1hi) 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+CD11bloF4/80hi) population in HO-1-/- kidneys compared with controls. Syngeneic transplant experiments utilizing green fluorescent protein-positive HO-1+/+ orHO-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.
  • Digital Object Identifier (doi)

    Author List

  • Hull TD; Kamal AI; Boddu R; Bolisetty S; Guo L; Tisher CC; Rangarajan S; Chen B; Curtis LM; George JF
  • Start Page

  • 2139
  • End Page

  • 2151
  • Volume

  • 26
  • Issue

  • 9