Filtration of chylomicrons by the liver may influence cholesterol metabolism and atherosclerosis

Fraser, Robin; Bosanquet, AG; Day, W.A.

doi:10.1016/0021-9150(78)90001-1

Cited by 79 publications

(46 citation statements)

References 18 publications

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“…73 The term "liver sieve" was first coined in 1978. 74 Its function was demonstrated in rat livers by the presence of larger chylomicrons in the sinusoidal blood compared with the smaller particles (remnants) observed in the space of Disse by transmission electron microscopy ( Fig. 7).…”

Section: Phase 11 (A): Role Of the Liver Sieve Inmentioning

confidence: 97%

Lipoproteins and the liver sieve: The role of the fenestrated sinusoidal endothelium in lipoprotein metabolism, atherosclerosis, and cirrhosis

1995

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The liver sieve, formed by the fenestrated hepatic sinusoidal endothelium, is a dynamic biofilter separating the hepatic blood from the plasma within the space of Disse. It filters macromolecules of differing sizes, especially lipoproteins. More specifically, it acts as a barrier to the large triglyceride-rich parent chylomicrons, while permitting the smaller triglyceride-depleted but cholesterol- and retinol-rich remnants to enter the space of Disse. There the remnants contact specific receptor sites on the hepatocyte microvilli. Thus, the liver sieve is the first site of hepatic selection and consequent metabolism of dietary cholesterol and fat-soluble vitamins, as well as rejection of dietary triglycerides. Therefore, perturbations of the porosity of the sieve, whether from changes in size, number of fenestrae, or composition of the underlying extracellular matrix within the space of Disse, will have a profound influence on the metabolism of lipoproteins. This disturbance of the homeostasis of lipids, including fat-soluble vitamins and cholesterol, as well as other macromolecules, may tilt the balance between health and disease in a variety of organs and tissues, such as the liver, kidney and arteries.

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Section: Phase 11 (A): Role Of the Liver Sieve Inmentioning

confidence: 97%

Lipoproteins and the liver sieve: The role of the fenestrated sinusoidal endothelium in lipoprotein metabolism, atherosclerosis, and cirrhosis

1995

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“…LSECs are perforated by fenestrations, which are pores approximately 100 nm in diameter grouped together in clusters known as liver sieve plates and occupying approximately 5% to 10% of the endothelial surface. 22 Fenestrations are true discontinuities in the endothelium, lacking either a diaphragm or underlying basal lamina.…”

mentioning

confidence: 99%

T lymphocytes interact with hepatocytes through fenestrations in murine liver sinusoidal endothelial cells

et al. 2006

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The liver has an established ability to induce tolerance. Recent evidence indicates that this unique property might be related to its distinctive architecture allowing T cells to be activated in situ independently of lymphoid tissues. Unlike lymph node-activated T cells, liver-activated T cells are shortlived, a mechanism that might contribute to the "liver tolerance effect." Although the potential role of hepatocytes as tolerogenic antigen-presenting cells has been demonstrated, the question as to whether these cells are able to interact with CD8 ؉ T cells in physiological settings remains controversial. Contradicting the immunological dogma stating that naïve T lymphocytes are prevented from interacting with parenchymal cells within non-lymphoid organs by an impenetrable endothelial barrier, we show here that the unique morphology of the liver sinusoidal endothelial cell (LSEC) permits interactions between lymphocytes and hepatocytes. Using electron microscopy, we demonstrate that liver resident lymphocytes as well as circulating naïve CD8 ؉ T cells make direct contact with hepatocytes through cytoplasmic extensions penetrating the endothelial fenestrations that perforate the LSECs. Furthermore, the expression of molecules required for primary T cell activation, MHC class I and ICAM-1, is polarized on hepatocytes to the perisinusoidal cell membrane, thus maximizing the opportunity for interactions with circulating lymphocytes. In conclusion, this study has identified, at the ultrastructural level, a unique type of interaction between naïve T lymphocytes and liver parenchymal cells in vivo. These results hold implications for the pathogenesis of viral hepatitis in which hepatocytes may represent the main antigen-presenting cell, and for the development of immune tolerance as lymphocytes pass through the liver.

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“…The fenestrae lumina constitute an open connection between the sinusoidal lumen and the space of Disse (Wisse, 1970;Wisse et al, 1985). One role of the fenestrae is filtration or sieving of the plasma (Fraser et al, 1978;Naito & Wisse, 1978;De Zanger & Wisse, 1982), allowing only fluid and particles smaller than the fenestrae to reach the parenchymal cells or to leave the space of Disse. By using scanning electron microscopy (SEM) it has been demonstrated that several agents modulate fenestrae diameter and number, in vivo and in vitro (for reviews see Arias, 1990;Smedsrød et al, 1994;Fraser et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Comparative atomic force and scanning electron microscopy: an investigation on fenestrated endothelial cells in vitro

Braet¹,

Kalle

Zanger³

et al. 1996

Journal of Microscopy

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SummaryRat liver sinusoidal endothelial cells (LEC) contain fenestrae, which are clustered in sieve plates. Fenestrae control the exchange of fluids, solutes and particles between the sinusoidal blood and the space of Disse, which at its back side is flanked by the microvillous surface of the parenchymal cells. The surface of LEC can optimally be imaged by scanning electron microscopy (SEM), and SEM images can be used to study dynamic changes in fenestrae by comparing fixed specimens subjected to different experimental conditions. Unfortunately, the SEM allows only investigation of fixed, dried and coated specimens. Recently, the use of atomic force microscopy (AFM) was introduced for analysing the cell surface, independent of complicated preparation techniques. We used the AFM for the investigation of cultured LEC surfaces and the study of morphological changes of fenestrae. SEM served as a conventional reference.AFM images of LEC show structures that correlate well with SEM images. Dried-coated, dried-uncoated and wetfixed LEC show a central bulging nucleus and flat fenestrated cellular processes. It was also possible to obtain height information which is not available in SEM. After treatment with ethanol or serotonin the diameters of fenestrae increased (6%) and decreased (ÿ15%), respectively. The same alterations of fenestrae could be distinguished by measuring AFM images of dried-coated, dried-uncoated and wet-fixed LEC. Comparison of dried-coated (SEM) and wetfixed (AFM) fenestrae indicated a mean shrinkage of 20% in SEM preparations. In conclusion, high-resolution imaging with AFM of the cell surface of cultured LEC can be performed on dried-coated, dried-uncoated and wet-fixed LEC, which was hitherto only possible with fixed, dried and coated preparations in SEM and transmission electron microscopy (TEM).

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Filtration of chylomicrons by the liver may influence cholesterol metabolism and atherosclerosis

Cited by 79 publications

References 18 publications

Lipoproteins and the liver sieve: The role of the fenestrated sinusoidal endothelium in lipoprotein metabolism, atherosclerosis, and cirrhosis

Lipoproteins and the liver sieve: The role of the fenestrated sinusoidal endothelium in lipoprotein metabolism, atherosclerosis, and cirrhosis

T lymphocytes interact with hepatocytes through fenestrations in murine liver sinusoidal endothelial cells

Comparative atomic force and scanning electron microscopy: an investigation on fenestrated endothelial cells in vitro

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