PRIMARY ROLE OF KUPFFER CELL-HEPATOCYTE COMMUNICATION IN THE EXPRESSION OF OXIDATIVE STRESS IN THE POSTISCHEMIC LIVER

It has been reported that hepatocyte metabolism and function can be mo dulated by the activated Kupffer cell through the release of different biomolecules like cytokines, eicosanoids, oxygen free radicals and en zymes. In relation to these paracrine factors involved in circuits of intercellular communication, the existence of a hepatic oxygen sensor located in the Kupffer cell has been postulated. According to this pos tulate the oxygen metabolism of the liver parenchymal cells could be u nder the control of the Kupffer cells. In order to study the role of t he Kupffer cell in the reperfusion syndrome of the liver, a lobular is chaemia-reperfusion model was performed in rats with or without previo us treatment with gadolinium chloride to block Kupffer cell function. Spontaneous chemiluminescence of the liver surface, oxygen uptake by t issue slices and tertbutyl hydroperoxide-initiated chemiluminescence d eterminations were performed to evaluate the oxygen metabolism and the oxy-radical generation by the liver. The lower basal photoemission, i n parallel with a lower basal oxygen uptake registered in the hepatic lobes from the animals pretreated with gadolinium chloride clearly ind icates that the gadolinium chloride-dependent functional inhibition of Kupffer cell leads to a downregulation of oxygen metabolism by the li ver. Moreover, the intensity of oxidative stress exhibited by the post ischaemic lobes appears to be closely linked with the Kupffer cell act ivity. On the basis of the data obtained we propose that a paracrine c ircuit between activated Kupffer cell and hepatocytes is an early key event in the induction of postischaemic oxidative stress in the liver. Furthermore the interference with the mitochondrial electron flow by some biomolecules released from rate of generation of reactive oxygen species by the inhibited mitochondrial respiratory chain. (C) 1998 Joh n Wiley & Sons, Ltd.