Uptake of liposomes containing phosphatidylserine by liver cells in vivo and by sinusoidal liver cells in primary culture: In vivo-in vitro differences

The interaction with liver cells of liposomes containing different mol frac tions of phosphatidylserine was investigated in vivo and in vitro. Increasi ng the amount of liposomal phosphatidylserine from 10 to 30 mol% leads to a faster blood disappearance of the liposomes. Within the liver, which is ma inly responsible for this elimination, these liposomes are only taken up by the hepatocytes and Kupffer cells. By contrast, sinusoidal endothelial cel ls, in vitro, do bind and internalize liposomes containing greater than or equal to 30% phosphatidylserine at least as actively as Kupffer cells. The uptake by endothelial and Kupffer cells is inhibited by poly-(inosinic acid ) and other anionic macromolecules, suggesting the involvement of scavenger receptors. The lack of liposome uptake by endothelial cells under in vivo conditions can be attributed to plasma effects since addition of various se ra caused severe reduction of in vitro uptake of liposomes. In vivo the pho sphatidylserine head groups may be masked by plasma proteins adsorbed to th e liposomal surface, thus preventing recognition by receptors, which are in trinsically able to recognize phosphatidylserine. (C) 1999 Academic Press.