Endotoxin impairs the engraftment of rat islets transplanted beneath the kidney capsule of C57BL/6-mice

The primary objective of this investigation was to determine the effect of endotoxin on islet xenograft survival within the first three days after tra nsplantation. Pancreatic isle ts from Lewis rats were prepared under endoto xin-free conditions with Liberase (Boehringer) and purified by centrifugati on on endotoxin-free Ficoll/Histopaque. After overnight incubation, with or without 10 mu g/ml endotoxin, the islets were transplanted beneath the kid ney capsule of normoglycemic C57Bl/6-mice. Three days later, kidneys were r emoved and their insulin content were measured. We could demonstrate signif icant differences (P<0.01) in insulin recovery between lipopolysaccharide-f ree and lipopolysaccharide-containing grafts. In case of endotoxin contamin ated islets, we found only 13+/-2% (n=9) of the original insulin content, i n contrast to 53+/-7% (n=9) when endotoxin-free islets where grafted. In ex periments with islets isolated by use of conventional (lipopolysaccharide-c ontaining) collagenase, and then cultured in endotoxin-free medium, insulin recovery three days after transplantation was 36+/-1% (n=13).