Induction of acute hepatic injury by endotoxin in mice

To investigate the changes of scavenger receptor (SR) and CD14 in Kupffer cells in endotoxemia in order to uncover the mechanism of the liver to turn a defense organ into effector one in sepsis.

Mouse models of endotoxemia of different severity were reproduced by injection of different doses of lipopolysaccharide (LPS) via the tail vein. The expression of SR and CD14 in the liver was assayed by immunohistochemistry and was subsequently analyzed with an image analysis system. The levels of TNF-alpha and IL-6 in liver tissue were determined with ELISA.

The expression of SR in the liver in the high-dose group was markedly decreased one hour after injection of LPS, and also in the low-dose group at 3 hours. The expression of SR in the liver in the two groups was shown to be progressively decreased with the time prolonged. There was significant difference in average optical density (OD) values of SR between the two groups. The expression of CD14 in the two groups was shown to be significantly increased one hour after injection of LPS, and more significantly with the time prolonged. But there was no significant difference in OD values of CD14 between the two groups. The contents of intrahepatic proinflammatory mediators TNF-alpha, IL-6, ALT and TBIL were significantly increased after injection of LPS. Correlation analysis revealed that the changes of TNF-alpha, IL-6, ALT, and TBIL were negatively correlated with the expression of SR, and positively with the expression of CD14.

The up-regulation of CD14 expression and down-regulation of SR expression on Kupffer cells might be one of the important mechanisms for the conversion of Kupffer cells from immune defensive to inflammatory response cells in acute hepatic injury.