Conditioned media of Kupffer and endothelial liver cells influence protein phosphorylation in parenchymal liver cells. Involvement of prostaglandins

Abstract

The possible role of Kupffer and endothelial liver cells in the regulation of parenchymal-liver-cell function was assessed by studying the influence of conditioned media of isolated Kupffer and endothelial cells on protein phosphorylation in isolated parenchymal cells. The phosphorylation state of three proteins was selectively influenced by the conditioned media. The phosphorylation state of an Mr-63,000 protein was decreased and the phosphorylation state of an Mr-47,000 and an Mr-97,000 protein was enhanced by these media. These effects could be mimicked by adding either prostaglandin E1, E2 or D2. Both conditioned media and prostaglandins stimulated the phosphorylase activity in parenchymal liver cells, suggesting that the Mr-97,000 phosphoprotein might be phosphorylase. Parenchymal liver cells secrete a phosphoprotein of Mr-63,000 and pI 5.0-5.5. The phosphorylation of this protein is inhibited by Kupffer- and endothelial-liver-cell media, and prostaglandins E1, E2 and D2 had a similar effect. The data indicate that Kupffer and endothelial liver cells secrete factors which influence the protein phosphorylation in parenchymal liver cells. This forms further evidence that products from non-parenchymal liver cells, in particular prostaglandin D2, might regulate glucose homoeostasis and/or other specific metabolic processes inside parenchymal cells. This stresses the concept of cellular communication inside the liver as a way by which the liver can rapidly respond to extrahepatic signals.

Precision-cut liver slices in culture as a tool to assess the physiological involvement of Kupffer cells in hepatic metabolism

“…By which mechanism PGE 2 could control lipid synthesis in the liver tissue? The phosphorylation rate of hepatic enzymes involved in the lipogenesis or cholesterogenesis pathways (acetyl-CoA synthetase, HMG-CoA-reductase) could be modulated by PGE 2 which is released at concentration sufficient to alter the phosphorylation of specific proteins inside the hepatocytes [12]. The use of indomethacin, known to inhibit prostaglandin production, in the incubation medium of PCLS could help to elucidate the role of PGE 2 released by Kupffer cell in the regulation of hepatic metabolism.…”

A new method to monitor Kupffer-cell function continuously in the perfused rat liver. Dissociation of glycogenolysis from particle phagocytosis

“…In addition, Kupffer cells produce a wide variety of chemical mediators which can kill other cells, including interferon, interleukin I, proteolytic enzymes and tumour necrosis factor (Nolan, 1981;Michie et al, 1988). Kupffer cells also synthesize leukotrienes and prostaglandins, which are important in mechanisms of cell movement and attachment (Nolan, 1981;Keppler et al, 1985), and in regulation of par-enchymal-cell function (Michie et al, 1988;Casteleijn et al, 1988a). Activation of Kupffer cells with endotoxin leads to an increase in cell size and number oflamellipodia (Nolan, 1981) and marked alterations in hepatic microcirculation (McCuskey et al, 1983).…”

Cellular communication inside the liver. Binding, conversion and metabolic effect of prostaglandin D2 on parenchymal liver cells

“…With isolated parenchymal liver cells it was found that prostaglandins were able to induce glycogenolysis [10], to change the degree of phosphorylation of three specific parenchymal-cell proteins [11] and to induce ornithine decarboxylase activity [6]. Among the various prostaglandins tested, PGD2 was found to be the most potent inducer of these effects, and we therefore suggested that PGD2 is the main eicosanoid involved in the intercellular communication between parenchymal and nonparenchymal liver cells [6,10,11].…”