We investigated the effect of the activation of complement in human serum on isolated adult porcine islets using an in vitro model of pig-to-human islet transplantation. Pancreata were obtained from slaughterhouse pigs (6-8 mo old). Islets were prepared by intraductal collagenase digestion followed by purification on Ficoll gradients. The purified islets were incubated with xenogeneic human serum with or without heat inactivation for 45 min. As control, islets were incubated with autologous porcine serum. After the incubation, the islets' responsiveness to an acute glucose stimulus (5.5 mM, static incubation) was evaluated by measurement of the insulin content of the medium. Islets exposed to human serum showed significantly lower insulin secretory response than the control (1.76 +/- 1.17 microU/islet/120 min, without heat inactivation; 1.74 +/- 1.36 microU/islet/120 min, with heat inactivation; 3.39 +/- 0.92 microU/islet/120 min, control). No difference in insulin secretory response, however, was observed between islets exposed to human serum with heat inactivation and without. Furthermore, we evaluated the cytotoxic activity of human serum on porcine islets by a complement-dependent cytotoxicity using the MTT colorimetric assay, and found that the human serum had no complement-dependent cytotoxic activity against the islets. We concluded that the insulin secretion dysfunction of porcine islets exposed to human serum was not due to the activation of complement and there was no evidence of hyperacute rejection mediated by complement activation in the in vitro model of pig-to-human islet transplantation.

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Predominant role of local immunosuppressive effect in enhanced efficacy of liposomal FK506 in organ transplantation.

Liposomal FK506 is a new formulation of FK506 that increases FK506 levels in the liver and decreases them in the kidney in comparison to conventional IV formulation. In the present study, the efficacy of liposomal FK506 was evaluated in canine kidney and liver transplantation models. Liposomal FK506 increased the immunosuppressive efficacy of FK506 in the liver transplantation model, but decreased it in the kidney transplantation model. These results suggest that local immunosuppressive effects with increased intragraft FK506 level would play an important role in enhancing the immunosuppressive efficacy of liposomal FK506 in liver transplantation.

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