Abstract |
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.
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Authors | Katja Kotsch, Paulo N A Martins, Roman Klemz, Uwe Janssen, Bernhard Gerstmayer, Annelie Dernier, Anja Reutzel-Selke, Ulrike Kuckelkorn, Stefan G Tullius, Hans-Dieter Volk |
Journal | Antioxidants & redox signaling
(Antioxid Redox Signal)
Vol. 9
Issue 12
Pg. 2049-63
(Dec 2007)
ISSN: 1523-0864 [Print] United States |
PMID | 17854277
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Biomarkers
- DNA, Complementary
- RNA, Messenger
- Carbon Monoxide
- Heme Oxygenase-1
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Topics |
- Animals
- Biomarkers
(metabolism)
- Carbon Monoxide
(metabolism)
- Cell Movement
- Cells, Cultured
- Cold Temperature
- DNA, Complementary
- Dendritic Cells
(physiology)
- Heme Oxygenase-1
(metabolism)
- Kidney Transplantation
(immunology, methods)
- Male
- Oligonucleotide Array Sequence Analysis
- Organ Preservation
(methods)
- Organ Transplantation
(adverse effects, methods)
- RNA, Messenger
(metabolism)
- Rats
- Rats, Inbred F344
- Rats, Inbred Lew
- Reperfusion Injury
(pathology, prevention & control)
- Time Factors
- Transplantation, Homologous
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