Induction of heme oxygenase-1 with cobalt protoporphyrin fails to prolong hamster-to-rat kidney xenograft survival
Introduction The anti-apoptotic gene heme oxygenase-1 (HO-1) is believed to be important in the development of accommodation of heart xenografts in the hamster-to-rat concordant model. Cobalt protoporphyrin (CoPP) is known to induce the expression of HO-1 in rodents. We attempted to prolong the survival of kidney xenografts in this model by up-regulating the expression of HO-1 in the donor organ with CoPP.
Materials and methods Male Lewis rats (175-225 g) underwent bilateral nephrectomy and received a single kidney transplant from a Golden Syrian hamster (125-165 g). The control animals received no treatment. One group of animals received daily intramuscular injections of cyclosporine A (5 mg/kg per day) beginning on the day of transplant. The third group received a kidney from a hamster treated with CoPP (10 mg/kg via intraperitoneal injection) 24 h prior to transplant. These recipients also received cyclosporine A (5 mg/kg per day i.m.). At the time of transplantation, the contralateral hamster kidney was removed and subjected to immunohistochemical analysis for HO-1. Animals experiencing operative complications (20%) were excluded from analysis. Rejection was defined as the death of the recipient.
Results Untreated control animals survived for a mean of 5.6 days (see Table). Those treated with cyclosporine A survived a mean of 6.2 days. The animals receiving the kidney pretreated with CoPP survived a mean of 6 days, despite immunohistochemical evidence that HO-1 expression had been up-regulated in the contralateral kidney.
Conclusions Up-regulation of HO-1 expression with cobalt protoporphyrin does not prolong survival of kidney xenografts in a hamster-to-rat model. Further studies are ongoing to determine if this observation is due to insufficient or inhomogeneous up-regulation of the gene, lack of protective effect of the gene, or is an organ-specific finding.