The role of beta2-glycoprotein I in liposome-hepatocyte interaction.
Adsorption of serum proteins to the liposomal surface plays a critical role in liposome clearance from the blood. The aim of this study was to investigate the role of liposome-adsorbed serum proteins in the interaction of liposomes with hepatocytes. We analyzed the serum proteins adsorbing to the surface of differently composed small unilamellar liposomes during incubation with human or rat serum, and found that one protein, with a molecular weight of around 55 kDa, adsorbed in a large amount to negatively charged liposomes containing phosphatidylserine (PS) or phosphatidylglycerol (PG). The binding was dependent on the liposomal charge density. The approximately 55-kDa protein was identified as beta2-glycoprotein I (beta2GPI) by Western blotting. Despite the high affinity of beta2GPI for strongly negatively charged liposomes, in vitro uptake and binding experiments with isolated rat hepatocytes, Kupffer cells or liver endothelial cells, and with HepG2 cells showed no enhancing effect of this protein on the association of negatively charged liposomes with any of these cells. On the contrary, an inhibitory effect was observed. We conclude that despite abundant adsorption to negatively charged liposomes, beta2GP1 inhibits, rather than enhances, liposome uptake by liver cells.
Yan
X
X
Groningen University Institute for Drug Exploration, Department of Cell Biology, University of Groningen, The Netherlands.
Morselt
H W M
HW
Scherphof
G L
GL
Poelstra
K
K
Kamps
J A A M
JA
D000327:Adsorption; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D042783:Endothelial Cells / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D007728:Kupffer Cells / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics*; D008099:Liver / Q000166:cytology; D008297:Male; D008970:Molecular Weight; D051381:Rats; D011919:Rats, Inbred Strains; D013499:Surface Properties; D053482:beta 2-Glycoprotein I
D001798:Blood Proteins; D006023:Glycoproteins; D008081:Liposomes; D053482:beta 2-Glycoprotein I