SIGNIFICANT INCREASE OF KUPFFER CELLS ASSOCIATED WITH LOSS OF NA-ATPASE ACTIVITY IN RAT HEPATIC ALLOGRAFT-REJECTION(,K+)

Background. Cholestasis is a complication that occurs during the rejec tion of liver transplants. The aim of this study was to investigate th e association of activated Kupffer cells (KCs) and Na+,K+-ATPase activ ity for taurocholate cotransport and bile canalicular (BC) Mg++-ATPase activity for hepatobiliary excretion in rat liver allograft. Methods. Quantitative analyses of KC number and size in relationship to enzyme activity of Na+,K+-ATPase and of BC Mg++-ATPase were conducted in rej ected liver after allogenic transplantation and after prevention of re jection using cyclosporine. Results. The animals were examined on the 10th postoperative day. In the rejection group, the number of KCs sign ificantly increased more than fourfold in comparison with the number o f KCs in the control livers. Some KCs were found in the sinusoids, but the majority were located in the space of Disse. Na+,K+-ATPase activi ty vanished from the basolateral plasma membrane, whereas BC Mg++-ATPa se activity was restored in the apical domain. With immunosuppression, KCs showed the same behavior as in the control group, and activity of both ATPases was observed as strong electron-dense precipitates in ba solateral and apical plasma membrane domains. Conclusions. In this stu dy, we demonstrate that activated KCs migrate into the donor liver and release cytokines, which leads to the loss of Na+,K+-ATPase activity in the rejection group. BC Mg++-ATPase activity was not influenced by these mediators of activated macrophages. Since Na+,K+-ATPase is the c otransporter for hepatocyte taurocholate uptake, these data may contri bute to understanding the mechanisms for cholestasis during hepatic al lograft rejection.