Heme oxygenase-1 ameliorates ischemia/reperfusion injury by targeting dendritic cell maturation and migration.
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.
Kotsch
Katja
K
Institute of Medical Immunology, Universitätsmedizin Charité Campus Mitte, Berlin, Germany. katja.kotsch@charite.de
Martins
Paulo N A
PN
Klemz
Roman
R
Janssen
Uwe
U
Gerstmayer
Bernhard
B
Dernier
Annelie
A
Reutzel-Selke
Anja
A
Kuckelkorn
Ulrike
U
Tullius
Stefan G
SG
Volk
Hans-Dieter
HD
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002248:Carbon Monoxide / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured; D003080:Cold Temperature; D018076:DNA, Complementary; D003713:Dendritic Cells / Q000502:physiology*; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D016030:Kidney Transplantation / Q000276:immunology / Q000379:methods; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D009926:Organ Preservation / Q000379:methods; D016377:Organ Transplantation / Q000009:adverse effects / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D013997:Time Factors; D014184:Transplantation, Homologous
D015415:Biomarkers; D018076:DNA, Complementary; D012333:RNA, Messenger; D002248:Carbon Monoxide; D051547:Heme Oxygenase-1