Lactosylceramide-induced stimulation of liposome uptake by Kupffer cells in vivo.
Incorporation of 8 mol percent lactosylceramide into small unilamellar vesicles consisting of cholesterol and sphingomyelin in an equimolar ratio and containing [3H] inulin as a marker resulted in an increase in total liver uptake and a drastic change in intrahepatic distribution of the liposomes after intravenous injection into rats. The control vesicles without glycolipid accumulated predominantly in the hepatocytes, but incorporation of the glycolipid resulted in a larger stimulation of Kupffer-cell uptake (3.2-fold) than of hepatocyte uptake (1.2-fold). Liposome preparations both with and without lactosylceramide in which part of the sphingomyelin was replaced by phosphatidylserine, resulting in a net negative charge of the vesicles, were cleared much more rapidly from the blood and taken up by the liver to higher extents. The negative charge had, however, no influence on the intrahepatic distributions. The fast hepatic uptake of the negatively charged liposomes allowed competition experiments with substrates for the galactose receptors on liver cells. Inhibition of blood clearance and liver uptake of lactosylceramide-containing liposomes by N-acetyl-D-galactosamine indicated the involvement of specific recognition sites for the liposomal galactose residues. This inhibitory effect of N-acetyl-D-galactosamine was shown to be mainly the result of a decreased liposome uptake by the Kupffer cells, compatible with the reported presence of a galactose specific receptor on this cell type (Kolb-Bachofen et al. (1982) Cell 29, 859-866). The difference between the results on sphingomyelin-based liposomes as described in this paper and those on phosphatidylcholine-based liposomes as published previously (Spanjer and Scherphof (1983) Biochim. Biophys. Acta 734, 40-47) are discussed.
D000116:Acetylgalactosamine / Q000494:pharmacology; D000818:Animals; D002784:Cholesterol / Q000502:physiology; D004727:Endothelium / Q000502:physiology; D006028:Glycosphingolipids / Q000502:physiology*; D007728:Kupffer Cells / Q000502:physiology*; D007790:Lactosylceramides / Q000502:physiology*; D008081:Liposomes; D008297:Male; D008563:Membrane Lipids / Q000502:physiology; D008657:Metabolic Clearance Rate; D010587:Phagocytosis; D051381:Rats; D013109:Sphingomyelins / Q000502:physiology
D006028:Glycosphingolipids; D007790:Lactosylceramides; D008081:Liposomes; D008563:Membrane Lipids; D013109:Sphingomyelins; D002784:Cholesterol; D000116:Acetylgalactosamine