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dc.contributor.authorØie, Cristina Ionica
dc.contributor.authorAppa, Rupa Shree
dc.contributor.authorHilden, Ida
dc.contributor.authorPetersen, Helle Heibroch
dc.contributor.authorGruhler, Albrecht
dc.contributor.authorSmedsrød, Bård
dc.contributor.authorHansen, John-Bjarne
dc.date.accessioned2012-03-27T12:50:50Z
dc.date.available2012-03-27T12:50:50Z
dc.date.issued2011
dc.description.abstractThe 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. To address this question, experiments were performed in vivo and in vitro to determine if receptor associated protein (RAP) and trypsin-activated α2-macroglobulin (α2M∗) were endocytosed in LSECs. 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 125I-RAP and 125I-α2M∗, whereas 5% and 11% were associated with LSECs. Uptake of RAP and α2M∗ in the different liver cell population in vitro was specific and followed by degradation. The uptake of 125I-RAP was not inhibited by ligands to known endocytosis receptors in LSECs, while uptake of 125I-α2M∗ 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 125I-RAP followed by mass spectrometry further confirmed and identified LRP-1 in LSECs. 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.en
dc.descriptionThis paper is part of Cristina Ionica Øie's doctoral thesis, which is available in Munin at <a href=http://hdl.handle.net/10037/2910>http://hdl.handle.net/10037/2910</a>en
dc.identifier.citationJournal of Hepatology 55(2011) nr. 6 s. 1346-1352en
dc.identifier.cristinIDFRIDAID 903761
dc.identifier.doidoi: 10.1016/j.jhep.2011.03.013
dc.identifier.issn0168-8278
dc.identifier.urihttps://hdl.handle.net/10037/4078
dc.identifier.urnURN:NBN:no-uit_munin_3798
dc.language.isoengen
dc.publisherMunksgaard Forlagen
dc.rights.accessRightsopenAccess
dc.subjectVDP::Medical disciplines: 700::Clinical medical disciplines: 750::Gastroenterology: 773en
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Gasteroenterologi: 773en
dc.titleRat liver sinusoidal endothelial cells (LSECs) express functional low density lipoprotein receptor-related protein-1 (LRP-1)en
dc.typeJournal articleen
dc.typeTidsskriftartikkelen
dc.typePeer revieweden


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