Heme oxygenase-1 ameliorates ischemia/reperfusion injury by targeting dendritic cell maturation and migration

Antioxid Redox Signal. 2007 Dec;9(12):2049-63. doi: 10.1089/ars.2007.1801.


Ischemia/reperfusion injury (IRI) has a major impact on short- and long-term renal allograft survival by increasing graft immunogenicity. Donor preconditioning by inducing heme oxygenase 1 (HO-1) has been proven to exert cytoprotective and antiinflammatory effects on the graft, thus resulting in reduced graft immunogenicity. The study analyzed the effects and mechanisms of HO-1-mediated cytoprotection in rat kidney transplants exposed to cold preservation. We studied the differential gene-expression patterns of allografts after either short or long cold ischemia using a customized cDNA microarray. Prolonged cold ischemia led, 12 h after engraftment, to enhanced levels of adhesion molecules, heat-shock proteins, chemokines (CXCL10), and a remarkable upregulation of immunoproteasomes. Next we addressed the question whether induction of HO-1 or its byproduct carbon monoxide (CO) in organ donors targets these candidate markers related to enhanced immunogenicity. Induction of HO-1 or CO in organ donors 24 h before organ harvesting resulted in reduced mRNA levels of immunoproteasomes, MHC class II expression, and co-stimulatory molecules in the recipient's spleen, suggesting diminished migration and activation of donor dendritic cells. This observation suggests that HO-1/CO induction protects marginal allografts by inhibiting the immunogenicity of donor-derived dendritic cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Carbon Monoxide / metabolism
  • Cell Movement*
  • Cells, Cultured
  • Cold Temperature
  • DNA, Complementary
  • Dendritic Cells / physiology*
  • Heme Oxygenase-1 / metabolism*
  • Kidney Transplantation / immunology
  • Kidney Transplantation / methods
  • Male
  • Oligonucleotide Array Sequence Analysis
  • Organ Preservation / methods
  • Organ Transplantation / adverse effects
  • Organ Transplantation / methods
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Inbred F344
  • Rats, Inbred Lew
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*
  • Time Factors
  • Transplantation, Homologous


  • Biomarkers
  • DNA, Complementary
  • RNA, Messenger
  • Carbon Monoxide
  • Heme Oxygenase-1