title: Rat liver sinusoidal endothelial cells (LSECs) express functional low density lipoprotein receptor-related protein-1 (LRP-1).
abstract: OBJECTIVE
  The low density lipoprotein receptor-related protein-1 (LRP-1) is a large, multifunctional endocytic receptor from the LDL receptor family, highly expressed in liver parenchymal cells (PCs), neurons, activated astrocytes, and fibroblasts. The aim of the study was to investigate if liver sinusoidal endothelial cells (LSECs), highly specialized scavenger cells, express LRP-1.
  
  
  METHODS
  To address this question, experiments were performed in vivo and in vitro to determine if receptor associated protein (RAP) and trypsin-activated α(2)-macroglobulin (α(2)M∗) were endocytosed in LSECs.
  
  
  RESULTS
  Both ligands were cleared from the circulation mainly by the liver. Hepatocellular distribution of intravenously administered ligands, assessed after magnetic bead cell separation using LSEC- and KC-specific antibodies, showed that PCs contained 93% and 82% of liver-associated (125)I-RAP and (125)I-α(2)M∗, whereas 5% and 11% were associated with LSECs. Uptake of RAP and α(2)M∗ in the different liver cell population in vitro was specific and followed by degradation. The uptake of (125)I-RAP was not inhibited by ligands to known endocytosis receptors in LSECs, while uptake of (125)I-α(2)M∗ was significantly inhibited by RAP, suggesting the involvement of LRP-1. Immunofluorescence using LRP-1 antibody showed positive staining in LSECs. Ligand blot analyses using total cell proteins and (125)I-RAP followed by mass spectrometry further confirmed and identified LRP-1 in LSECs.
  
  
  CONCLUSIONS
  LSECs express functional LRP-1. An important implication of our findings is that LSECs contribute to the rapid removal of blood borne ligands for LRP-1 and may thus play a role in lipid homeostasis.
authors.affiliation: Center for Atherothrombotic Research in Tromsø, Department of Medicine, Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway. cristina.ionica.oie@uit.no
authors.forename: Cristina Ionica
authors.initials: CI
authors.lastname: Øie
authors.forename: Rupa Shree
authors.initials: RS
authors.lastname: Appa
authors.forename: Ida
authors.initials: I
authors.lastname: Hilden
authors.forename: Helle Heibroch
authors.initials: HH
authors.lastname: Petersen
authors.forename: Albrecht
authors.initials: A
authors.lastname: Gruhler
authors.forename: Bård
authors.initials: B
authors.lastname: Smedsrød
authors.forename: John-Bjarne
authors.initials: JB
authors.lastname: Hansen
mesh_terms: D000818:Animals; D004705:Endocytosis; D042783:Endothelial Cells / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D026563:LDL-Receptor Related Protein-Associated Protein / Q000378:metabolism; D008024:Ligands; D008099:Liver / Q000166:cytology* / Q000378:metabolism*; D008102:Liver Circulation; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000511:alpha-Macroglobulins / Q000378:metabolism
chemical_list: D026563:LDL-Receptor Related Protein-Associated Protein; D008024:Ligands; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D012333:RNA, Messenger; D000511:alpha-Macroglobulins