Liver sinusoidal endothelial cells depend on mannose receptor-mediated recruitment of lysosomal enzymes for normal degradation capacity

Elvevold, Kjetil; Simón-Santamaría, Jaione; Hasvold, Hege; McCourt, Peter; Smedsrød, Bård; Sørensen, Karen Kristine

doi:10.1002/hep.22527

Cited by 79 publications

(92 citation statements)

References 41 publications

(68 reference statements)

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“…In contrast, for 125 I-JC-VLP, the liver-associated radioactivity decreased from 60% to 30% of total recovered radioactivity during the same time period ( Figure 3B ), indicating effective hepatocellular degradation of JC-VLP. A corresponding increase of radioactivity in the gastrointestinal tract (including mesenterium and lymph nodes) and the rest of carcass in the same period was judged to be caused by redistribution of degradation products, which is commonly noted following administration of 125 I-labeled ligands [26].…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, LSECs express Fc gamma-receptor IIb2 [20], [21], which mediates endocytosis of soluble immune complexes, and other receptors involved in virus uptake such as L-SIGN [22] and LSECtin [23]. Ligands eliminated from blood mainly by LSECs, and to a lesser by Kupffer cells (resident liver macrophages), include connective tissue turnover products, lysosomal enzymes [13], [15],[24]–[26]), modified plasma proteins and lipoproteins [27]–[30], soluble IgG immune complexes [31], yeast mannan [32], and adenovirus/adenoviral vectors [7],[33]. Differently to macrophages, LSECs operate essentially via clathrin-mediated endocytosis, and not by phagocytosis, and the cells are equipped with an endocytic machinery capable of super-efficient uptake and degradation of the internalized ligands [10], [34].…”

Section: Introductionmentioning

confidence: 99%

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Efficient Uptake of Blood-Borne BK and JC Polyomavirus-Like Particles in Endothelial Cells of Liver Sinusoids and Renal Vasa Recta

et al. 2014

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Liver sinusoidal endothelial cells (LSECs) are specialized scavenger cells that mediate high-capacity clearance of soluble waste macromolecules and colloid material, including blood-borne adenovirus. To explore if LSECs function as a sink for other viruses in blood, we studied the fate of virus-like particles (VLPs) of two ubiquitous human DNA viruses, BK and JC polyomavirus, in mice. Like complete virions, VLPs specifically bind to receptors and enter cells, but unlike complete virions, they cannot replicate. 125I-labeled VLPs were used to assess blood decay, organ-, and hepatocellular distribution of ligand, and non-labeled VLPs to examine cellular uptake by immunohisto- and -cytochemistry. BK- and JC-VLPs rapidly distributed to liver, with lesser uptake in kidney and spleen. Liver uptake was predominantly in LSECs. Blood half-life (∼1 min), and tissue distribution of JC-VLPs and two JC-VLP-mutants (L55F and S269F) that lack sialic acid binding affinity, were similar, indicating involvement of non-sialic acid receptors in cellular uptake. Liver uptake was not mediated by scavenger receptors. In spleen, the VLPs localized to the red pulp marginal zone reticuloendothelium, and in kidney to the endothelial lining of vasa recta segments, and the transitional epithelium of renal pelvis. Most VLP-positive vessels in renal medulla did not express PV-1/Meca 32, suggesting location to the non-fenestrated part of vasa recta. The endothelial cells of these vessels also efficiently endocytosed a scavenger receptor ligand, formaldehyde-denatured albumin, suggesting high endocytic activity compared to other renal endothelia. We conclude that LSECs very effectively cleared a large fraction of blood-borne BK- and JC-VLPs, indicating a central role of these cells in early removal of polyomavirus from the circulation. In addition, we report the novel finding that a subpopulation of endothelial cells in kidney, the main organ of polyomavirus persistence, showed selective and rapid uptake of VLPs, suggesting a role in viremic organ tropism.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Efficient Uptake of Blood-Borne BK and JC Polyomavirus-Like Particles in Endothelial Cells of Liver Sinusoids and Renal Vasa Recta

et al. 2014

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“…The following findings in the present study point to the To obtain direct evidence for identification of LRP-1 in LSECs and thereby rule out possible influence of marginal contamination of PCs, the cell cultures were pre-incubated 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 18 with TRITC-FSA, a ligand that is known to be taken up only by the LSECs in the liver [12]. KCs.…”

Section: Lrp-1 Expression In Liver Cellsmentioning

confidence: 99%

Rat liver sinusoidal endothelial cells (LSECs) express functional low density lipoprotein receptor-related protein-1 (LRP-1)

Øie

Appa

Hilden

et al. 2011

Journal of Hepatology

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“…CS cultures do not incorporate non-parenchymal cells (NPCs), which are critical in maintaining liver homeostasis, 1 while 2D cocultures fail to capture the stratified cellular arrangement found in vivo. An organotypic hepatic model should contain all three cell types since hepatocytes, LSECs, and KCs carry out several important and complementary functions in the liver, including metabolism and detoxification (hepatocytes), 1 clearance of toxins and waste, 10 and production of cytokines and phagocytosis. 1,11 There is a growing recognition that hepatic cell cultures should mimic the in vivo structure of the liver.…”

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confidence: 99%

Designing a Multicellular Organotypic 3D Liver Model with a Detachable, Nanoscale Polymeric Space of Disse

Larkin

Rodrigues²,

Murali³

et al. 2013

Tissue Engineering Part C: Methods

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The design of in vitro models that mimic the stratified multicellular hepatic microenvironment continues to be challenging. Although several in vitro hepatic cultures have been shown to exhibit liver functions, their physiological relevance is limited due to significant deviation from in vivo cellular composition. We report the assembly of a novel three-dimensional (3D) organotypic liver model incorporating three different cell types (hepatocytes, liver sinusoidal endothelial cells, and Kupffer cells) and a polymeric interface that mimics the Space of Disse. The nanoscale interface is detachable, optically transparent, derived from self-assembled polyelectrolyte multilayers, and exhibits a Young's modulus similar to in vivo values for liver tissue. Only the 3D liver models simultaneously maintain hepatic phenotype and elicit proliferation, while achieving cellular ratios found in vivo. The nanoscale detachable polymeric interfaces can be modulated to mimic basement membranes that exhibit a wide range of physical properties. This facile approach offers a versatile new avenue in the assembly of engineered tissues. These results demonstrate the ability of the tri-cellular 3D cultures to serve as an organotypic hepatic model that elicits proliferation and maintenance of phenotype and in vivo-like cellular ratios.

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Liver sinusoidal endothelial cells depend on mannose receptor-mediated recruitment of lysosomal enzymes for normal degradation capacity

Cited by 79 publications

References 41 publications

Efficient Uptake of Blood-Borne BK and JC Polyomavirus-Like Particles in Endothelial Cells of Liver Sinusoids and Renal Vasa Recta

Efficient Uptake of Blood-Borne BK and JC Polyomavirus-Like Particles in Endothelial Cells of Liver Sinusoids and Renal Vasa Recta

Rat liver sinusoidal endothelial cells (LSECs) express functional low density lipoprotein receptor-related protein-1 (LRP-1)

Designing a Multicellular Organotypic 3D Liver Model with a Detachable, Nanoscale Polymeric Space of Disse

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