The role of apolipoprotein E in the elimination of liposomes from blood by hepatocytes in the mouse.
We evaluated the role of apolipoprotein E (apoE) in the clearance of neutral and negatively charged liposomes by hepatocytes in apoE-deficient mice. Negatively charged liposomes were cleared at identical rates in apoE-deficient and wild-type mice; neutral liposomes were cleared at a 3.6-fold slower rate in apoE-deficient mice. ApoE deficiency did not affect hepatic uptake of negatively charged liposomes but lowered that of neutral liposomes >5-fold. Hepatocyte uptake of neutral liposomes was reduced >20-fold in apoE-deficient mice; that of negatively charged liposomes remained unchanged. We conclude that uptake of neutral liposomes by hepatocytes is nearly exclusively apoE-mediated.
Yan
Xuedong
X
Department of Cell Biology, Department of Pharmacokinetics and Drug Delivery, Department of Pathology and Laboratory Medicine, [corrected] Medical Biology Section, Groningen University Institute for Drug Exploration (GUIDE), The Netherlands.
Kuipers
Folkert
F
Havekes
Louis M
LM
Havinga
Rick
R
Dontje
Bert
B
Poelstra
Klaas
K
Scherphof
Gerrit L
GL
Kamps
Jan A A M
JA
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000378:metabolism*; D002478:Cells, Cultured; D022781:Hepatocytes / Q000378:metabolism*; D008081:Liposomes / Q000097:blood* / Q000493:pharmacokinetics*; D008099:Liver / Q000098:blood supply / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D009928:Organ Specificity; D014018:Tissue Distribution
D001057:Apolipoproteins E; D008081:Liposomes