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Inhibition of ischemia/reperfusion injury and chronic graft deterioration by a single-donor treatment with cobalt-protoporphyrin for the induction of heme oxygenase-1
- Source :
- Scopus-Elsevier
- Publication Year :
- 2002
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2002.
-
Abstract
- Today, the major problem in organ transplantation is not acute graft rejection but chronic graft deterioration. In addition to alloantigen-specific events, alloantigen independent factors like donor age, previous diseases, consequences of brain death, and perioperative events of ischemia/reperfusion injury have a major impact on long-term graft function. The induction of the stress protein heme oxygenase-1 (HO-1) protects cells from injury and apoptosis. Here, we tested the protective effects of HO-1 induction in a clinically relevant kidney transplant model. Induction of HO-1 expression following cobalt-protoporphyrin (CoPP) treatment in organ donors prolonged graft survival and long-term function remarkably following extended periods of ischemia. Positive effects were observed with both optimal and marginal grafts from old donor animals. Structural changes characteristic for chronic rejection, as well as graft infiltration by monocytes/macrophages and CD8+ T cells, were substantially reduced following HO-1 induction. Up-regulation of HO-1 expression before organ transplantation was also associated with reduced levels for tumor necrosis factor (TNF)-alpha mRNA, increased levels for interferon (IFN)-gamma, and bcl-x, and insignificant differences for CD25, interleukin (IL)-2, IL-4, IL-6, and IL-10 mRNA levels. The significant improvement of long-term graft function following induction of HO-1 expression in donor organs suggests that this strategy may be a novel clinical treatment option with particular relevance for transplantation of marginal organs.
- Subjects :
- Male
medicine.medical_specialty
Transcription, Genetic
T-Lymphocytes
Ischemia
Protoporphyrins
Pharmacology
Gene Expression Regulation, Enzymologic
Organ transplantation
Animals
Medicine
RNA, Messenger
Treatment Failure
Transplantation
business.industry
Interleukins
Interleukin
Receptors, Interleukin-2
Cobalt
medicine.disease
Kidney Transplantation
COPP
Rats, Inbred F344
Rats
Heme oxygenase
surgical procedures, operative
Rats, Inbred Lew
Enzyme Induction
Reperfusion Injury
Heme Oxygenase (Decyclizing)
Immunology
Tumor necrosis factor alpha
business
Reperfusion injury
Heme Oxygenase-1
Subjects
Details
- ISSN :
- 00411337
- Volume :
- 74
- Database :
- OpenAIRE
- Journal :
- Transplantation
- Accession number :
- edsair.doi.dedup.....f04774b1407e09c38bb012af90890134