C-Peptide determinations in islet xenotransplantation: A study in the pig-to-mouse model.
Assays of C-peptide are used to monitor allogeneic islet graft function. However, it is not known whether xenogeneic C-peptide is metabolized and excreted in a fashion similar to endogenous and allogeneic C-peptide. In this study, injection of 10 times the physiological amount of porcine C-peptide into mice did not result in the excretion of the C-peptide in the urine. In contrast, when a physiological amount of porcine C-peptide was injected into athymic mice, urinary excretion of porcine C-peptide was readily detected. After injection of radioactively labeled porcine C-peptide into mice, the radioactive uptake in tissues belonging to the mononuclear phagocytic system was significantly increased in mice immunized towards the xenogeneic C-peptide. These results may reflect an immunological reactivity towards the C-peptide. Antibodies against porcine C-peptide could not be detected in the serum of any of the mice. However, porcine C-peptide was found to be glycosylated. Thus, a possible explanation to the lack of porcine C-peptide in the urine is that xenoreactive antibodies had bound to carbohydrate structures on the peptide and that the antibody-C-peptide complex had been cleared from the circulation by the mononuclear phagocytic system. Thus, the urinary excretion of xenogeneic C-peptide seems to be different from that of endogenous and allogeneic C-peptide. Consequently, determinations of donor-specific C-peptide may not properly reflect islet xenograft function. In fact, islet xenograft function may be underestimated.
Wennberg
L
L
Department of Transplantation Surgery, Karolinska Institute, Huddinge Hospital, Sweden. lars.wennberg@transpl.hs.sll.se
Sundberg
B
B
Ekdahl-Nilsson
K
K
Korsgren
O
O
D000818:Animals; D002096:C-Peptide / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D018929:Cell Culture Techniques / Q000379:methods; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000601:surgery*; D016332:Fetal Tissue Transplantation / Q000502:physiology*; D006031:Glycosylation; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D007515:Islets of Langerhans / Q000166:cytology* / Q000196:embryology; D016381:Islets of Langerhans Transplantation / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D013370:Subrenal Capsule Assay; D013552:Swine; D014018:Tissue Distribution; D014183:Transplantation, Heterologous / Q000502:physiology*
D002096:C-Peptide; D007457:Iodine Radioisotopes