Endotoxins inhibit endocytotic catabolism of low‐density lipoproteins in Hep G2 cells

The effects of endotoxins on the uptake and degradation of low‐density lipoproteins in Hep G2, a welldifferentiated human hepatoma cell line, were studied. The results showed that incubation of Hep G2 cells with 125 I‐labeled low‐density lipoprotein in the presence of endotoxins caused decreased uptake and degradation of 125 I‐labeled low‐density lipoprotein. The inhibitory effects of endotoxins on the uptake and degradation of 125 I‐labeled low‐density lipoprotein were dose and time dependent. With a monoclonal low‐density lipoprotein receptor antibody, it was found that endotoxins interfered with both low‐density lipoprotein receptor–mediated and non‐low‐density lipoprotein receptor–mediated uptake. If, however, the cells were pretreated with endotoxins for 1 or 24 hr and then incubated with new medium without endotoxins, no inhibitory effect on the subsequent uptake and degradation of 125 I‐labeled low‐density lipoprotein occurred. Endotoxins had no toxic effects on Hep G2 cells as judged by [ 3 H]thymidine incorporation and by determination of cell growth. Also, endotoxins did not under our experimental conditions induce oxidative modification of low‐density lipoprotein. Furthermore, reisolated low‐density lipoprotein that had previously been incubated with endotoxin was catabolized to a lower extent by Hep G2 cells than was control lowdensity lipoprotein. We speculate that the inhibitory effect of endotoxins on cellular low‐density lipoprotein catabolism is due to the formation of endotoxin–lowdensity lipoprotein complexes, which interfere with the binding of low‐density lipoprotein to the cell surface. (H EPATOLOGY 1992;16:224–231.)