Differential abilities of mouse liver parenchymal and nonparenchymal cells in HDL and LDL (native and oxidized) association and cholesterol efflux

2006 ◽  
Vol 84 (2) ◽  
pp. 250-256 ◽  
Author(s):  
Jany Lapointe ◽  
To Quyen Truong ◽  
Louise Falstrault ◽  
Louise Brissette
Keyword(s):  
Mouse Liver ◽  
Cholesterol Efflux ◽  
Oxidized Ldl ◽  
Density Lipoprotein ◽  
Selective Uptake ◽  
Liver Parenchymal ◽  
Nonparenchymal Cells ◽  
Uptake Activity ◽  
Iodine 125 ◽  
Parenchymal Cells

The aim of this study was to quantify the abilities of mouse liver parenchymal and nonparenchymal cells with respect to (i) cholesteryl ester (CE) selective uptake from low-density lipoproteins (LDL), oxidized LDL (OxLDL), and high-density lipoprotein (HDL); and (ii) their free cholesterol efflux to HDL. The preparations of cells were incubated with lipoproteins labelled either in protein with iodine-125 or in CE with 3H-cholesterol oleate, and lipoprotein-protein and lipoprotein-CE associations were measured. The associations of LDL-protein and LDL-CE with nonparenchymal cells were 5- and 2-fold greater, respectively, than with parenchymal cells. However, in terms of CE-selective uptake (CE association minus protein association) both types of cell were equivalent. Similar results were obtained with OxLDL, but both types of cell showed higher abilities in OxLDL-CE than in LDL-CE selective uptake (on average by 3.4-fold). The association of HDL-protein with nonparenchymal cells was 3× that with parenchymal cells; however, nonparenchymal cells associated 45% less HDL-CE. Contrary to parenchymal cells, nonparenchymal cells did not show HDL-CE selective uptake activity. Thus parenchymal cells selectively take CE from the 3 types of lipoproteins, whereas nonparenchymal cells exert this function only on LDL and OxLDL. Efflux was 3.5-fold more important in nonparenchymal than in parenchymal cells.Key words: LDL, HDL, parenchymal, SR-BI, CD36, selective uptake, cholesterol.

scholarly journals Scavenger receptor B1 (SR-B1) substrates inhibit the selective uptake of high-density-lipoprotein cholesteryl esters by rat parenchymal liver cells

1997 ◽  
Vol 326 (2) ◽  
pp. 515-519 ◽  
Author(s):  
Kees FLUITER ◽  
Theo J. C. van BERKEL
Keyword(s):  
High Density Lipoprotein ◽  
Rat Liver ◽  
Oxidized Ldl ◽  
Scavenger Receptor ◽  
Density Lipoprotein ◽  
High Density ◽  
Cholesteryl Esters ◽  
Selective Uptake ◽  
Liver Parenchymal ◽  
Parenchymal Cells

High-density lipoprotein cholesteryl esters (HDL-CE) are selectively taken up by liver parenchymal cells without parallel apolipoprotein uptake, and this selective uptake route forms an important step in reverse cholesterol transport. Recent data from Acton, Rigotti, Landschulz, Xu, Hobbs and Krieger [(1996) Science 271, 518–520] provide evidence that scavenger receptor B (SR-B1) can mediate selective uptake of HDL-CE. In order to identify if selective uptake of HDL-CE by rat liver parenchymal cells can be mediated by a protein with scavenger receptor properties we performed competition experiments in vivo with substrates for scavenger receptors. Addition of either low-density lipoprotein (LDL), acetylated LDL (AcLDL) or oxidized LDL (OxLDL) only marginally (< 10%) decreased the association of HDL particles to parenchymal cells as measured by 125I-labelled HDL. HDL-CE association was inhibited by AcLDL by 35%, while addition of OxLDL did inhibit HDL-CE association by 80%, thereby completely blocking the selective uptake of HDL-CE. Studies with HDL labelled with a fluorescent cholesteryl-ester analogue confirmed that OxLDL mediated complete inhibition of HDL-CE selective uptake by rat liver parenchymal cells. The inhibition of HDL-CE selective uptake by OxLDL was insensitive to the additional presence of polyinosinic acid (poly I), indicating that the inhibitory effect did not involve a poly I-sensitive site. Anionic phospholipid liposomes inhibited HDL-CE association by 40%, while neutral liposomes were ineffective. The inhibition of the selective uptake of HDL-CE in liver parenchymal cells by modified LDL, in particular OxLDL and anionic phospholipids suggests that, in liver, the SR-B1 is responsible for the efficient uptake of HDL-CE.

scholarly journals Low-density-lipoprotein receptors in different rabbit liver cells

1989 ◽  
Vol 261 (2) ◽  
pp. 587-593 ◽  
Author(s):  
M S Nenseter ◽  
O Myklebost ◽  
R Blomhoff ◽  
C A Drevon ◽  
A Nilsson ◽  
...  
Keyword(s):  
Kupffer Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Binding Activity ◽  
Rabbit Liver ◽  
Low Density ◽  
Apo B ◽  
Liver Parenchymal ◽  
Ldl Binding ◽  
Parenchymal Cells

Receptor-dependent uptake mechanisms for low-density lipoprotein (LDL) were studied in rabbit liver parenchymal and non-parenchymal cells. Hybridization studies with a cDNA probe revealed that mRNA for the apo (apolipoprotein) B,E receptor was present in endothelial and Kupffer cells as well as in parenchymal cells. By ligand-blotting experiments we showed that apo B,E-receptor protein was present in both parenchymal and non-parenchymal cells. Studies of binding of homologous LDL in cultured rabbit parenchymal cells suggested that about 63% of the specific LDL binding was mediated via the apo B,E receptor. Approx. 47% of the specific LDL binding was dependent on Ca2+, suggesting that specific Ca2+-dependent as well as Ca2+-independent LDL-binding sites exist in liver parenchymal cells. Methylated LDL bound to the parenchymal cells in a saturable manner. Taken together, our results showed that apo B,E receptors are present in rabbit liver endothelial and Kupffer cells as well as in the parenchymal cells, and that an additional saturable binding activity for LDL may exist on rabbit liver parenchymal cells. This binding activity was not inhibited by EGTA or reductive methylation of lysine residues in apo B. LDL degradation in parenchymal cells was mainly mediated via the apo B,E receptor.

scholarly journals Activation of the TLR4 signaling pathway and abnormal cholesterol efflux lead to emphysema in ApoE-deficient mice

2012 ◽  
Vol 302 (11) ◽  
pp. L1200-L1208 ◽  
Author(s):  
Monica Goldklang ◽  
Polina Golovatch ◽  
Tina Zelonina ◽  
Jordis Trischler ◽  
Daniel Rabinowitz ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Oxidized Ldl ◽  
Interleukin 1 ◽  
Low Density Lipoprotein ◽  
Airflow Obstruction ◽  
Density Lipoprotein ◽  
Atherogenic Diet ◽  
Lung Damage ◽  
Increased Risk ◽  
Density Lipoprotein Receptor

Smokers with airflow obstruction have an increased risk of atherosclerosis, but the relationship between the pathogenesis of these diseases is not well understood. To determine whether hypercholesterolemia alters lung inflammation and emphysema formation, we examined the lung phenotype of two hypercholesterolemic murine models of atherosclerosis at baseline and on a high-fat diet. Airspace enlargement developed in the lungs of apolipoprotein E-deficient (Apoe −/− ) mice exposed to a Western-type diet for 10 wk. An elevated number of macrophages and lymphocytes accompanied by an increase in matrix metalloproteinase-9 (MMP-9) activity and MMP-12 expression was observed in the lungs of Apoe −/− mice on a Western-type diet. In contrast, low-density lipoprotein receptor-deficient ( Ldlr −/−) mice did not exhibit lung destruction or inflammatory changes. Most importantly, we revealed augmented expression of the downstream targets of the Toll-like receptor (TLR) pathway, interleukin-1 receptor-associated kinase 1, and granulocyte colony-stimulating factor, in the lungs of Apoe −/− mice fed with a Western-type diet. In addition, we demonstrated overexpression of MMP-9 in Apoe −/− macrophages treated with TLR4 ligand, augmented with the addition of oxidized LDL, suggesting that emphysema in these mice results from the activation of the TLR pathway secondary to known abnormal cholesterol efflux. Our findings indicate that, in Apoe −/− mice fed with an atherogenic diet, abnormal cholesterol efflux leads to increased systemic inflammation with subsequent lung damage and emphysema formation.

scholarly journals Selective uptake of cholesteryl esters from apolipoprotein-E-free high-density lipoproteins by rat parenchymal cells in vivo is efficiently coupled to bile acid synthesis

1991 ◽  
Vol 280 (2) ◽  
pp. 359-365 ◽  
Author(s):  
M N Pieters ◽  
D Schouten ◽  
H F Bakkeren ◽  
B Esbach ◽  
A Brouwer ◽  
...  
Keyword(s):  
Bile Acid ◽  
Cholesteryl Ester ◽  
Bile Acids ◽  
Density Lipoprotein ◽  
Cholesteryl Oleate ◽  
Cholesteryl Esters ◽  
Liver Uptake ◽  
Selective Uptake ◽  
Parenchymal Cells ◽  
Kinetics Of

[3H]Cholesteryl ester-labelled human high-density lipoprotein (HDL) was injected into rats and its decay, intrahepatic cellular distribution and the kinetics of biliary secretion were determined. At 10 min after injection the hepatic uptake of cholesteryl esters from HDL was 3-fold higher as compared with the apolipoprotein. Selective uptake was exerted only by parenchymal cells (5.6-fold more cholesteryl esters than apolipoprotein) and not by liver endothelial or Kupffer cells. The kinetics of biliary secretion of processed cholesteryl esters initially associated with HDL or low-density lipoprotein (LDL) were compared in unrestrained rats, equipped with permanent catheters in bile duct, duodenum and heart. At 72 h after injection of [3H]cholesteryl oleate-labelled HDL, 51.0 +/- 2.5% of the injected dose was recovered as bile acids, which is about twice as high as the secretion of biliary radioactivity after injection of [3H]cholesteryl oleate-labelled LDL. Oestradiol treatment stimulated only liver uptake of LDL cholesteryl esters, and resulted in a 2-fold higher liver uptake than with HDL. However, the rate of radioactive bile acid formation from [3H]cholesteryl oleate-labelled HDL was still more rapid than for LDL. It is concluded that the selective uptake pathway for cholesteryl esters from HDL in parenchymal cells is more efficiently coupled to the formation of bile acids than is the cholesteryl ester uptake from LDL. This efficient coupling may facilitate the role of HDL in reverse cholesterol transport.

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