KUPFFER CELLS DEPRESS HEPATOCYTE PROTEIN-SYNTHESIS ON COLD-STORAGE OFTHE RAT-LIVER

The causes of liver failure after transplantation are multifactorial. An understanding of the mechanisms of injury to the liver could help t o define methods to improve preservation and transplantation. We measu red protein synthesis by SH-leucine incorporation into acid precipitab le protein in rat liver tissue slices, isolated hepatocytes, and isola ted perfused liver (IPL) after cold storage for 24 or 48 hr in Univers ity of Wisconsin (UW) solution. Some rats were pretreated with dexamet hasone prior to liver harvest. Protein synthesis was depressed in all in vitro models after 24 hr storage. The percent decrease was greater in tissue slices and IPL (about 70% decrease relative to fresh livers) than in isolated hepatocytes (about 30% decrease). Dexamethasone pret reatment improved protein synthesis significantly after 24 hr preserva tion in tissue slices and in IPL, but had no significant effect on pro tein synthesis in isolated hepatocytes. The greater loss of protein sy nthesis in tissue slices and IPL compared with that in isolated hepato cytes was considered in relation to the presence of Kupffer cells in t he former systems and lack of Kupffer cells in the isolated cell suspe nsions. Kupffer cells generate cytotoxins that could cause injury to m etabolically depressed hepatocytes or endothelial cells. Dexamethasone has been shown to modulate Kupffer cell inhibition of hepatocyte func tions. The results suggest that preservation damage to hepatocytes sen sitizes them to further damage on reperfusion by Kupffer cell-generate d agents.