Changes of plasma oxidized low-density lipoprotein levels during endotoxemia and its effect on Kupffer's cell response to LPS

Objective To investigate the kinetics of plasma oxidized low density lipoprotein levels (Ox LDL) in endotoxemia, and the effect of Ox LDL on Kupffer cell(KC) response to lipopolysaccharide (LPS) stimulation. Methods Intravenous injection of 1, 5 or 10 mg/kg LPS induced rat models of endotoxemia. Plasma Ox LDL level was assayed by using ELISA kit. KCs isolated from mice were cultured and then pretreated with Ox LDL(10 - 100 μg/ml) or anti SR mAb(10 μg/ml) or anti CD14 mAb ( 10 μg/ml ) plus Ox LDL(100 μg/ml) for 1 h before LPS stimulation. Supernatants were collected 3 hours after LPS challenge for TNF α assay. Results Plasma Ox LDL levels increased significantly in all of the three groups after injection of LPS, in which the 10 mg/kg group increased most significantly. Pretreatment of KC with Ox LDL could markedly enhance the LPS induced activation of KCs, as shown by increased levels of TNF α in supernatants. This enhancement of Ox LDL was in dose dependent manner, and similar to the effect of anti SR mAb on KC response to LPS. Anti CD14 mAb could completely inhibit LPS induced activation of KCs. Conclusions This experiment indicates that plasma Ox LDL levels can significantly increase at the early stage of endotoxemia in a dose dependent manner. Ox LDL can significantly enhance LPS induced activation of KCs, which may be related to promotion of LPS binding to CD14 on the surface of KCs by Ox LDL.