Clearance of gut-derived endotoxins by the liver. Release and modification of 3H, 14C-lipopolysaccharide by isolated rat Kupffer cells.

This paper describes experiments that were designed to study postuptake modification by isolated rat Kupffer cells of a 3H,14C-biosynthetically labeled endotoxin purified from Escherichia coli J5 as assessed by cesium chloride isopyknic density gradients and gel permeation chromatography. Pulse-chase experiments demonstrated that half as much of the endotoxin's lipid, relative to polysaccharide, was released by the cells. Density gradients revealed that native endotoxin equilibrated at a density of 1.412 g/ml, whereas endotoxin retained by Kupffer cells equilibrated at densities of 1.274 and 1.295 g/ml. Gel permeation chromatography indicated that endotoxin retained by Kupffer cells formed a larger micelle than either exocytosed or native endotoxin. Endotoxin exocytosed by Kupffer cells fractionated into two peaks, one with a smaller and one with a larger apparent micelle size than native endotoxin but both smaller than the retained lipopolysaccharide. Both systems indicated that the Kupffer cell modified endotoxin by enriching the lipid content of the molecule and shortening the length of the O-antigen. Thus, the Kuffer cell, in its mode of action on the endotoxin molecule, appears to play a prominent role in the initial phase of a biochemical process for endotoxin clearance and detoxification.