Portal Vein Transfusion Increases Pancreatic Islet Allograft Survival in Mice

PURPOSE: Considering the complications of nonspecific immunosuppression, as well as the availability of insulin, heavy immunosuppressive treatment to pancreatic islet transplantation patients is not justified. Antigen administration via the portal vein has been demonstrated to induce immunosuppression, and may present a possible mechanism for the induction of tolerance. Using a mouse model, without any immunosuppressive treatment, the islet allograft survivals were compared between portal venous transfusion and portal venous saline injection groups. METHODS: Six C57BL/6J mice were used as pancreatic islet donors per Balb/c recipient mouse. Islets were harvested by digestion of the pancreata with collagenase, with subsequent Ficoll density gradient separation. Recipient mice were divided into two groups: seven mice received a portal venous injection of 0.1 cc saline (PVS) and eight a portal venous transfusion of 0.1 cc donor blood (PVT). Islets were transplanted into the subcapsular space of the left kidney. Transplantation failure was determined if the transplanted mouse failed to show a blood glucose level less than 200 mg/dl at 24 hours after the transplantation; these mice were not included in the statistics. Rejection was determined when the normalized blood glucose level (<200 mg/dl) returned to above 300 mg/dl. RESULTS: The mean islet equivalent numbers (IEQ) of the seven PVS and eight PVT mice were 893+/-262 and 911+/-288, respectively. The islet allograft survival of the PVS group ranged between 1 to 9 days; whereas, that of the PVT group ranged between 6 to 16 days. The PVT group showed significantly higher islet allograft survival than the PVS group (P=0.0443). CONCLUSION: A portal venous transfusion prolonged the islet allograft survival.

Expression of MIP-1alpha mRNA in Kupffer Cells and Serum MIP-1alpha Post Portal Vein Transfusion / 대한이식학회지

PURPOSE: Portal vein transfusion (PVT) has been known to induce immunosuppression or tolerance and Kupffer cell was identified to play an important role in the phenomenon. The purposes of this study were investigating PVT effect on gene regulation in Kupffer cells and subsequent change in serum cytokine. METHODS: For investigating the effect of PVT, Kupffer cells were isolated from the mice (BalbC) of six groups; 1 hour sham operation (S), 1 hour portal vein saline injection (PVS), 1 hour PVT, 24 hour S, 24 hour PVS, and 24 hour PVT groups. Each group was composed of 3 mice. Total RNAs isolated from Kupffer cells were subjected to RT-PCR differential display. The bands of 24 hour group showing increased expression was cloned for the sequencing analysis. RESULTS: Macrophage inflammatory protein 1 alpha (MIP-1alpha) was identified from the bands of increased expression. In PVT groups, increased expression of MIP-1alpha mRNA in Kupffer cells coincided with elevated serum level of MIP-1alpha. CONCLUSION: MIP-1alpha may be one of the important cytokines involved in PVT induced immunosuppression or tolerance.