A coculture model of intrahepatic islet transplantation: activation of Kupffer cells by islets and acinar tissue

Clinical and experimental studies of intrahepatic islet transplantation hav e allowed histological and systemic observations to be made, but the locati on of the transplanted islets makes it difficult to assess direct effects o n the cells of the liver. An in vitro coculture model of Kupffer cells with islets or pancreatic acinar tissue is described, using porcine tissue and measuring the secretion of thromboxane B-2, prostaglandin E-2, 6-keto-prost aglandin F-1 alpha, and prostaglandin F-2 alpha as an indicator of Kupffer cell stimulation. The results have demonstrated activation of Kupffer cells in the presence of acinar or islet tissue, both when the cells were in dir ect contact and when separated by a membrane. This indicated that the stimu lation was due to a soluble factor or factors, and was confirmed by the cul ture of Kupffer cells with acinar conditioned medium. The degree of stimula tion was much greater with acinar tissue than with islets. In subsequent ex periments, aprotinin, an enzyme activation inhibitor, was added to the cocu ltures in an attempt to reduce Kupffer cell activation. This had no effect, possibly due to the fact that the endogenous pancreatic enzymes may alread y be activated during digestion of the pancreas. Aprotinin alone caused an increase in secretion of eicosanoids from Kupffer cells. The high response to acinar tissue is of particular relevance to islet autotransplantation in which unpurified pancreatic digest is often transplanted. The clinical eff ectiveness of aprotinin in the light of these results is discussed. In conc lusion, although unable to mimic the complex situation following intrahepat ic islet transplantation. the coculture model described here allows the opp ortunity to assess the events relating to specific cell types. and will pro vide the scope to undertake more detailed studies on the mechanisms involve d. The same model could be applied to the coculture of pancreatic tissue wi th hepatocytes to determine any effects on the normal function of hepatocyt es.