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Elvevold, Kjetil; Nedredal, Geir I.; Revhaug, Arthur; Smedsrød, Bård

doi:10.1186/1476-5926-3-4

Cited by 52 publications

(16 citation statements)

References 50 publications

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“…LSECs represent a highly specialized type of scavenger endothelium preserved across different vertebrate species including rodents and humans [10], [45]. Several signature characteristics are the same in LSECs across mammals: Cell morphology and endocytosis receptor expression in human LSECs are identical to that of rodents and pig [10], [11], [15], [43], [44], and the scavenger function of rat, mouse, and pig LSECs is strikingly similar [64]. It is therefore likely that our present findings on the efficient LSEC endocytosis of polyoma VLPs in mice reflect the fate of these viruses also in human livers.…”

Section: Discussionmentioning

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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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: Discussionmentioning

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 capacity of LSECs to possess several of the properties seen in DCs, such as the expression of MHC class II, various co-stimulatory molecules, and CD11c and their ability to activate naive T cells has been reported 60–68 . LSECs can take up antigen using a multitude of receptors 69 . The question as to whether a) LSECs are efficient APCs and b) can induce T-cell tolerance has also been addressed systematically.…”

Section: Liver-related Antigen Presenting Cells In Immunity and Tolermentioning

confidence: 99%

“…The endothelium of liver sinusoids is discontinued (fenestrated) and is formed by a layer of liver sinusoidal endothelial cells 16 . These cells act as scavenger cells and form a physical filtering barrier between the sinusoidal blood and plasma 69, 391 . Kupffer cells are resident macrophages, that are attached to the layer of liver sinusoidal endothelial cells.…”

Section: Figurementioning

confidence: 99%

Liver Immunology

Bogdanos

Gao

Gershwin

2013

Comprehensive Physiology

175

130

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The liver is the largest organ in the body and is generally regarded by non-immunologists as not having lymphoid function. However, such is far from accurate. This review highlights the importance of the liver as a lymphoid organ. Firstly, we discuss experimental data surrounding the role of liver as a lymphoid organ. The liver facilitates a tolerance rather than immunoreactivity, which protects the host from antigenic overload of dietary components and drugs derived from the gut and is also instrumental to fetal immune tolerance. Loss of liver tolerance leads to autoaggressive phenomena which if are not controlled by regulatory lymphoid populations may lead to the induction of autoimmune liver diseases. Liver-related lymphoid subpopulations also act as critical antigen-presenting cells. The study of the immunological properties of liver and delineation of the microenvironment of the intrahepatic milieu in normal and diseased livers provides a platform to understand the hierarchy of a series of detrimental events which lead to immune-mediated destruction of the liver and the rejection of liver allografts. The majority of emphasis within this review will be on the normal mononuclear cell composition of the liver. However, within this context, we will discus select, but not all, immune mediated liver disease and attempt to place these data in the context of human autoimmunity.

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“…They provide a porous barrier between blood components and liver parenchymal cells, i.e., hepatocytes. Moreover their endocytic capacities make them effective scavengers for molecules such as albumin, acetylated low-density lipoproteins (Ac-LDL) and antigens in the bloodstream [ 1 , 2 ].…”

Section: Introductionmentioning

confidence: 99%

Methods for Isolation and Purification of Murine Liver Sinusoidal Endothelial Cells: A Systematic Review

et al. 2016

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To study the biological functions of liver sinusoidal endothelial cells (LSEC) and to identify their interplay with blood or liver cells, techniques allowing for the isolation and purification of LSEC have been developed over the last decades. The objective of the present review is to summarize and to compare the efficiency of existing methods for isolating murine LSEC. Toward this end, the MEDLINE database was searched for all original articles describing LSEC isolation from rat and mouse livers. Out of the 489 publications identified, 23 reported the main steps and outcomes of the procedure and were included in our review. Here, we report and analyse the technical details of the essential steps of the techniques used for LSEC isolation. The correlations between the prevalence of some steps and the efficiency of LSEC isolation were also identified. We found that centrifugal elutriation, selective adherence and, more recently, magnetic-activated cell sorting were used for LSEC purification. Centrifugal elutriation procured high yields of pure LSEC (for rats 30–141.9 million cells for 85–98% purities; for mice 9–9.25 million cells for >95% purities), but the use of this method remained limited due to its high technical requirements. Selective adherence showed inconsistent results in terms of cell yields and purities in rats (5–100 million cells for 73.7–95% purities). In contrast, magnetic-activated cell sorting allowed for the isolation of highly pure LSEC, but overall lower cell yields were reported (for rats 10.7 million cells with 97.6% purity; for mice 0.5–9 million cells with 90–98% purities). Notably, the controversies regarding the accuracy of several phenotypic markers for LSEC should be considered and their use for both magnetic sorting and characterization remain doubtful. It appears that more effort is needed to refine and standardize the procedure for LSEC isolation, with a focus on the identification of specific antigens. Such a procedure is required to identify the molecular mechanisms regulating the function of LSEC and to improve our understanding of their role in complex cellular processes in the liver.

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Cited by 52 publications

References 50 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

Liver Immunology

Methods for Isolation and Purification of Murine Liver Sinusoidal Endothelial Cells: A Systematic Review

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