On the mechanism of hepatic transendothelial passage of large liposomes

Liposomes of 400 nm in diameter can cross the 100-nm fenestrations in the e ndothelium of the hepatic sinusoid, provided they contain phosphatidylserin e (PS) but not phosphatidylglycerol CPG) [Daemen et al. (1997) Hepatology 2 6, 416]. We present evidence indicating that (i) the PS effect does not inv olve a pharmacological action of this lipid on the size of the fenestration s, (ii) fluid-type but not solid-type PS liposomes have access to the hepat ocytes and (iii) the lack of uptake of PG liposomes by hepatocytes is not d ue to a lack of affinity of the hepatocytes for PG surfaces. We conclude th at the mechanism responsible for the uptake of large PS-containing liposome s by hepatocytes in vivo involves a mechanical deformation of these liposom es during their passage across the endothelial fenestrations. (C) 1999 Fede ration of European Biochemical Societies.