Uptake of canine beta-very low density lipoproteins by mouse peritoneal macrophages is mediated by a low density lipoprotein receptor.

Koo, Catherine H.; Wernette-Hammond, M E; Innerarity, Thomas L.

doi:10.1016/s0021-9258(18)67367-3

Cited by 119 publications

(16 citation statements)

References 40 publications

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“…Competition studies provide evidence that on mouse macrophages the recognition of ,-VLDL is presumably exerted by the (unusual) LDL receptor [9,10]. The data presented are in perfect accordance with the data published previously by Koo et al [9] and Ellsworth et al [10], and actually our conditions for performing competition studies are based on their original finding that /,-VLDL is recognized by macrophages by the LDL receptor which possesses a low competitive affinity for LDL. Also, for Hep G2 cells we found that the binding of 125I-/J-VLDL (1 jtg/ml) is completely inhibited by an excess of LDL.…”

Section: Discussionsupporting

confidence: 89%

“…The observation that /1-VLDL binding correlates directly with the amount of LDL receptors has led to the conclusion that in macrophages a socalled unusual LDL receptor is the predominant, if not the only, receptor responsible for fl-VLDL binding. This receptor differs from the classical LDL receptor described in human fibroblasts in its low affinity for LDL and its relative resistance to downregulation by extracellular cholesterol [8][9][10].…”

Section: Introductionmentioning

confidence: 61%

“…The characteristics of the ,3-VLDL interaction with rat parenchymal cells (absence of competition with a 500-fold excess of LDL, Ca2+-independent binding, absence of down-regulation, slight effect of antibodies against the LDL receptor) indicate that the high-affinity binding of ,-VLDL is not exerted by the classical or unusual LDL receptor [9,10]. This conclusion is in accordance with the difficulty of showing the presence of a LDLspecific recognition site in liver from untreated rats [29,40].…”

Section: Discussionmentioning

confidence: 96%

“…The interaction of ,-VLDL with macrophages has been described in a number of studies, and it has been shown that the uptake of this lipoprotein is mediated via a high-affinity receptor, which is related to the LDL (apo B,E) receptor [8][9][10]. This receptor requires Ca2+ for optimal binding of ,-VLDL, whereas the cell association of radiolabelled ,-VLDL can be competed for by both unlabelled ,-VLDL and LDL.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of the low-density-lipoprotein-receptor-independent interaction of β-very-low-density lipoprotein with rat and human parenchymal liver cells in vitro

Water

Kamps

Dijk

et al. 1992

Biochemical Journal

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beta-Migrating very-low-density lipoprotein (beta-VLDL) is a cholesteryl-ester-enriched lipoprotein which under normal conditions is rapidly cleared by parenchymal liver cells. In this study the characteristics of the interaction of beta-VLDL with rat parenchymal cells, Hep G2 cells and human parenchymal cells are evaluated. The binding of beta-VLDL to these cells follows saturation kinetics (Bmax. respectively 117, 106 and 103 ng of beta-VLDL apoliprotein/mg of cell protein), with a relatively high affinity (Kd respectively for beta-VLDL of 10.7, 5.1 and 8.4 micrograms/ml). Competition studies of unlabelled beta-VLDL, low-density lipoprotein (LDL) or acetylated LDL with the binding of radiolabelled beta-VLDL indicate that a LDL-receptor-independent, Ca(2+)-independent, specific recognition site for beta-VLDL is present on rat and human parenchymal cells, whereas with Hep G2 cells or mouse macrophages beta-VLDL recognition is performed by the LDL receptor. The binding of beta-VLDL to Hep G2 cells was down-regulated by 89% by prolonged exposure to beta-VLDL, whereas for human parenchymal and rat parenchymal cells down-regulation of 44% and 20% respectively was observed. Studies with antibodies against the LDL receptor support the presence of a LDL-receptor-independent specific beta-VLDL recognition site on rat and human parenchymal cells. It is concluded that a LDL-receptor-independent recognition site for beta-VLDL is present on rat and human parenchymal liver cells. The presence of a LDL-receptor-independent recognition site on human parenchymal cells may mediate in vivo the uptake of beta-VLDL during consumption of a cholesterol-rich diet, when LDL receptors are down-regulated, thus protecting against the extrahepatic accumulation of the atherogenic beta-VLDL constituents.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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Characterization of the low-density-lipoprotein-receptor-independent interaction of β-very-low-density lipoprotein with rat and human parenchymal liver cells in vitro

Water

Kamps

Dijk

et al. 1992

Biochemical Journal

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“…The lipoproteins which interact with macrophages bind to specific cell surface receptors and enter the cell by the process of receptor-mediated endocytosis (4). Interestingly, there is considerable evidence to suggest that LDL, which poorly stimulates ACAT, and/3-VLDL, which is a potent stimulator of ACAT, enter mouse peritoneal macrophages by the same receptor (9,21). This receptor is a protein that is very similar to the human fibroblast LDL, or apo-B,E, receptor (9,21).…”

mentioning

confidence: 99%

Endocytosed beta-VLDL and LDL are delivered to different intracellular vesicles in mouse peritoneal macrophages.

Tabas

Lim

et al. 1990

The Journal of Cell Biology

117

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Hypercholesterolemic rabbit beta-VLDL and human LDL are both internalized by mouse peritoneal macrophages by receptor-mediated endocytosis. However, only beta-VLDL (which binds to the cells with a much higher affinity than LDL) markedly stimulates acyl-CoA/cholesterol acyl transferase (ACAT) and induces foam cell formation in these cells. As an initial step to test whether the two lipoproteins might be targeted to different organelles (which might differ in their ability to deliver cholesterol to microsomal ACAT), we studied the endocytic pathways of beta-VLDL and LDL. Lipoproteins were labeled with the non-transferable fluorescent label, DiI. When the macrophages were incubated with DiI-LDL for 10 min at 37 degrees C, the fluorescence was concentrated near the center of the cell both in heavily labeled vesicles and in a diffuse pattern. The pattern with DiI-beta-VLDL was quite different: an array of bright vesicles throughout the cytoplasm was the predominant feature. Differences in distribution were seen as early as 2 min of incubation and persisted throughout a 10-min chase period. By using a procedure in which photobleaching of DiI fluorescence converts diaminobenzidine into an electron-dense marker, we were able to identify at the ultrastructural level vesicles containing electron-dense material in cells incubated with DiI-beta-VLDL. Human E2/E2 beta-VLDL (from a patient with familial dysbetalipoproteinemia), which has a binding affinity and ACAT-stimulatory potential similar to LDL, gave a pattern of fluorescence virtually identical to LDL. Pulse-chase studies with 125I-labeled and [3H]cholesteryl ester-labeled lipoproteins disclosed that both protein degradation and cholesteryl ester hydrolysis were markedly retarded in beta-VLDL compared with LDL. Thus, in mouse peritoneal macrophages, endocytosed beta-VLDL appears in a distinct set of widely-distributed vesicles not seen with LDL (or with E2-beta-VLDL) and, compared with LDL, has a markedly diminished rate of protein degradation and cholesteryl ester hydrolysis. The differential routing of LDL and beta-VLDL may provide a mechanism for differences in ACAT-stimulatory potential between the two lipoproteins.

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Lipoproteins and Atherogenesis

Steinberg

Witztum²

1990

JAMA

433

102

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Uptake of canine beta-very low density lipoproteins by mouse peritoneal macrophages is mediated by a low density lipoprotein receptor.

Cited by 119 publications

References 40 publications

Characterization of the low-density-lipoprotein-receptor-independent interaction of β-very-low-density lipoprotein with rat and human parenchymal liver cells in vitro

Characterization of the low-density-lipoprotein-receptor-independent interaction of β-very-low-density lipoprotein with rat and human parenchymal liver cells in vitro

Endocytosed beta-VLDL and LDL are delivered to different intracellular vesicles in mouse peritoneal macrophages.

Lipoproteins and Atherogenesis

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