Cellular and subcellular distribution of injected lipopolysaccharide in rat liver and its inactivation by bile salts.

The cellular and subcellular distribution of biologically tritiated Salmonella abortus equi lipopolysaccharide (LPS) was studied at different time intervals after intravenous injection in rats. At 1 min after injection of LPS via the portal vein label was present over Kupffer cell phagosomes. Between 30 min and 7 days after injection, silver grains were mainly associated with phagosomes and lysosomes and occasionally with the membrane of Kupffer cells. A few parenchymal cells were labeled at 5 min in their mitochondria, cell membrane and the periphery of the cell. Radioactivity was also present in the rough endoplasmic reticulum (from 15 min), fat droplets and the nucleus (from 3 h) up to 7 days. Sinusoidal endothelial and fat-storing cells were never labeled. In conclusion, both Kupffer cells and parenchymal cells play a role in the uptake of LPS by the liver. The uptake and processing of endotoxin is rapid, since label is found early after administration and radioactivity is detected in the bile within 1 h. This radioactivity represents non-detoxified LPS, since it is lethal for galactosamine-sensitised mice after extraction with hot phenol/water. However, in the presence of bile salts, the LPS is non-lethal and not capable of clotting the limulus amebocyte lysate. LPS injection causes bile flow reduction within 45 min.