Expression of heme oxygenase-1 can determine cardiac xenograft survival
| Autor: | Robert B. Colvin, Koichiro Sato, Shane T. Grey, Josef Anrather, Fritz H. Bach, Eva Csizmadia, Miguel P. Soares, Ko Takigami, Yuan Lin, Augustine M.K. Choi, Kenneth D. Poss |
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| Rok vydání: | 1998 |
| Předmět: |
Graft Rejection
Bilirubin medicine.medical_treatment Transplantation Heterologous Apoptosis Biology General Biochemistry Genetics and Molecular Biology Mice chemistry.chemical_compound Transcription (biology) Cyclosporin a medicine Animals Gene Heme Elapid Venoms chemistry.chemical_classification Complement Inactivator Proteins Mice Inbred BALB C Myocardium Graft Survival Membrane Proteins Immunosuppression General Medicine Rats DNA-Binding Proteins Mice Inbred C57BL Heme oxygenase Enzyme chemistry Heme Oxygenase (Decyclizing) Immunology Cyclosporine Cancer research Heart Transplantation Heme Oxygenase-1 Immunosuppressive Agents |
| Zdroj: | Nature Medicine. 4:1073-1077 |
| ISSN: | 1546-170X 1078-8956 |
| DOI: | 10.1038/2063 |
| Popis: | The rejection of concordant xenografts, such as mouse-to-rat cardiac xenografts, is very similar to the delayed rejection of porcine-to-primate discordant xenografts1,2,3,4,5,6. In concordant models, this type of rejection is prevented by brief complement inhibition by cobra venom factor (CVF) and sustained T-cell immunosuppression by cyclosporin A (CyA) (refs. 7,8,9,10 ). Mouse hearts that survive indefinitely in rats treated with CVF plus CyA express the anti-inflammatory gene heme oxygenase-1 (HO-1) in their endothelial cells and smooth muscle cells9,11,12,13,14. The anti-inflammatory properties of HO-1 are thought to rely on the ability of this enzyme to degrade heme and generate bilirubin, free iron and carbon monoxide15. Bilirubin is a potent anti-oxidant13, free iron upregulates the transcription of the cytoprotective gene, ferritin16, and carbon monoxide is thought to be essential in regulating vascular relaxation in a manner similar to nitric oxide15. We show here that the expression of the HO-1 gene is functionally associated with xenograft survival, and that rapid expression of HO-1 in cardiac xenografts can be essential to ensure long-term xenograft survival. |
| Databáze: | OpenAIRE |
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