Hepatocellular clearance function of bacterial lipopolysaccharides and free lipid A in mice with endotoxic shock

Hepatic uptake of bacterial lipopolysaccharides (LPS) in defined salt forms and free lipid A was studied in C3H mice. Extracts of 14C-labeled and unlabeled LPS from Salmonella abortus equi and lipid A from Salmonella minnesota R 595 (Re) were administered intravenously in doses sufficient to induce endotoxic shock. Sixty minutes after administration of 14C-LPS, 40% of the total activity was found in the liver tissue, 10% was in the isolated nonparenchymal cells, and only 1% was in the isolated hepatocytes. However, at this time only one third of the hepatocytes could be isolated; the other two thirds were obviously damaged. After 240 minutes, 55% of the total activity was measured in the liver tissue. The nonparenchymal cells had 8% of the activity, and all hepatocytes were damaged. By use of immunofluorescence, LPS S abortus equi was localized in sinusoidal cells 5 to 10 minutes after administration, and LPS S minnesota R 595 and lipid A were found in both nonparenchymal and parenchymal liver cells. All toxins were localized in both cell populations 60 and 240 minutes after injection. After application of LPS or lipid A, the third complement component (C3) was detectable in sinusoidal cells. In decomplemented mice the hepatic deposits of LPS and lipid A were unaffected, without demonstration of C3. The data indicate that LPS and lipid A interact in vivo with Kupffer cells and hepatocytes. Hepatic clearance of endotoxin seems to be independent of complement.