scholarly journals The Scavenger Function of Liver Sinusoidal Endothelial Cells in Health and Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Sabin Bhandari ◽  
Anett Kristin Larsen ◽  
Peter McCourt ◽  
Bård Smedsrød ◽  
Karen Kristine Sørensen
Keyword(s):  
Endothelial Cells ◽  
Cell Activation ◽  
Biological Activities ◽  
High Capacity ◽  
Great Majority ◽  
Blood Clearance ◽  
Liver Sinusoidal Endothelial Cells ◽  
Sinusoidal Endothelial Cells ◽  
Waste Products ◽  
Health And Disease

The aim of this review is to give an outline of the blood clearance function of the liver sinusoidal endothelial cells (LSECs) in health and disease. Lining the hundreds of millions of hepatic sinusoids in the human liver the LSECs are perfectly located to survey the constituents of the blood. These cells are equipped with high-affinity receptors and an intracellular vesicle transport apparatus, enabling a remarkably efficient machinery for removal of large molecules and nanoparticles from the blood, thus contributing importantly to maintain blood and tissue homeostasis. We describe here central aspects of LSEC signature receptors that enable the cells to recognize and internalize blood-borne waste macromolecules at great speed and high capacity. Notably, this blood clearance system is a silent process, in the sense that it usually neither requires or elicits cell activation or immune responses. Most of our knowledge about LSECs arises from studies in animals, of which mouse and rat make up the great majority, and some species differences relevant for extrapolating from animal models to human are discussed. In the last part of the review, we discuss comparative aspects of the LSEC scavenger functions and specialized scavenger endothelial cells (SECs) in other vascular beds and in different vertebrate classes. In conclusion, the activity of LSECs and other SECs prevent exposure of a great number of waste products to the immune system, and molecules with noxious biological activities are effectively “silenced” by the rapid clearance in LSECs. An undesired consequence of this avid scavenging system is unwanted uptake of nanomedicines and biologics in the cells. As the development of this new generation of therapeutics evolves, there will be a sharp increase in the need to understand the clearance function of LSECs in health and disease. There is still a significant knowledge gap in how the LSEC clearance function is affected in liver disease.

scholarly journals Liver Sinusoidal Endothelial Cells Contribute to Hepatic Antigen-Presenting Cell Function and Th17 Expansion in Cirrhosis

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1227
Author(s):  
Esther Caparrós ◽  
Oriol Juanola ◽  
Isabel Gómez-Hurtado ◽  
Amaya Puig-Kroger ◽  
Paula Piñero ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
T Cell ◽  
Bile Duct ◽  
T Cell Activation ◽  
Cell Activation ◽  
Experimental Models ◽  
Cd4 T Cell ◽  
Liver Sinusoidal Endothelial Cells ◽  
Sinusoidal Endothelial Cells ◽  
Bacterial Peritonitis

Hepatic immune function is compromised during cirrhosis. This study investigated the immune features of liver sinusoidal endothelial cells (LSECs) in two experimental models of cirrhosis. Dendritic cells, hepatic macrophages, and LSECs were isolated from carbon tetrachloride and bile duct-ligated rats. Gene expression of innate receptors, bacterial internalization, co-stimulatory molecules induction, and CD4+ T cell activation and differentiation were evaluated. Induced bacterial peritonitis and norfloxacin protocols on cirrhotic rats were also carried out. LSECs demonstrated an active immunosurveillance profile, as shown by transcriptional modulation of different scavenger and cell-adhesion genes, and their contribution to bacterial internalization. LSECs significantly increased their expression of CD40 and CD80 and stimulated CD4+ T cell activation marker CD71 in both models. The pro-inflammatory Th17 subset was expanded in CCl4-derived LSECs co-cultures. In the bile duct ligation (BDL) model, CD4+ T cell differentiation only occurred under induced bacterial peritonitis conditions. Differentiated pro-inflammatory Th cells by LSECs in both experimental models were significantly reduced with norfloxacin treatment, whereas Foxp3 tolerogenic Th CD4+ cells were expanded. Conclusion: LSECs’ participation in the innate-adaptive immune progression, their ability to stimulate pro-inflammatory CD4+ T cells expansion during liver damage, and their target role in norfloxacin-induced immunomodulation granted a specific competence to this cell population in cirrhosis.

scholarly journals SECs (Sinusoidal Endothelial Cells), Liver Microenvironment, and Fibrosis

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Vaishaali Natarajan ◽  
Edward N. Harris ◽  
Srivatsan Kidambi
Keyword(s):  
Endothelial Cells ◽  
Liver Fibrosis ◽  
Cell Activation ◽  
Stellate Cell ◽  
Protein Profile ◽  
Liver Sinusoidal Endothelial Cells ◽  
Sinusoidal Endothelial Cells ◽  
Fibrotic Liver ◽  
Nonalcoholic Fatty Liver ◽  
Functional Features

Liver fibrosis is a wound-healing response to chronic liver injury such as alcoholic/nonalcoholic fatty liver disease and viral hepatitis with no FDA-approved treatments. Liver fibrosis results in a continual accumulation of extracellular matrix (ECM) proteins and paves the way for replacement of parenchyma with nonfunctional scar tissue. The fibrotic condition results in drastic changes in the local mechanical, chemical, and biological microenvironment of the tissue. Liver parenchyma is supported by an efficient network of vasculature lined by liver sinusoidal endothelial cells (LSECs). These nonparenchymal cells are highly specialized resident endothelial cell type with characteristic morphological and functional features. Alterations in LSECs phenotype including lack of LSEC fenestration, capillarization, and formation of an organized basement membrane have been shown to precede fibrosis and promote hepatic stellate cell activation. Here, we review the interplay of LSECs with the dynamic changes in the fibrotic liver microenvironment such as matrix rigidity, altered ECM protein profile, and cell-cell interactions to provide insight into the pivotal changes in LSEC physiology and the extent to which it mediates the progression of liver fibrosis. Establishing the molecular aspects of LSECs in the light of fibrotic microenvironment is valuable towards development of novel therapeutic and diagnostic targets of liver fibrosis.

scholarly journals Human Host Defense Cathelicidin Peptide LL-37 Enhances the Lipopolysaccharide Uptake by Liver Sinusoidal Endothelial Cells without Cell Activation

2016 ◽  
Vol 196 (3) ◽  
pp. 1338-1347 ◽  
Author(s):  
Kaori Suzuki ◽  
Taisuke Murakami ◽  
Zhongshuang Hu ◽  
Hiroshi Tamura ◽  
Kyoko Kuwahara-Arai ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Host Defense ◽  
Cell Activation ◽  
Liver Sinusoidal Endothelial Cells ◽  
Sinusoidal Endothelial Cells ◽  
Human Host

scholarly journals Angiocrine signaling in the hepatic sinusoids in health and disease

2016 ◽  
Vol 311 (2) ◽  
pp. G246-G251 ◽  
Author(s):  
Enis Kostallari ◽  
Vijay H. Shah
Keyword(s):  
Endothelial Cells ◽  
Cell Activation ◽  
Stellate Cell ◽  
Cell Types ◽  
Hepatocyte Proliferation ◽  
Liver Sinusoidal Endothelial Cells ◽  
Functional Changes ◽  
Liver Zonation ◽  
Health And Disease ◽  
Short Synthesis

The capillary network irrigating the liver is important not only for nutrient and oxygen delivery, but also for the signals distributed to other hepatic cell types necessary to maintain liver homeostasis. During development, endothelial cells are a key component in liver zonation. In adulthood, they maintain hepatic stellate cells and hepatocytes in quiescence. Their importance in pathobiology is highlighted in liver regeneration and chronic liver diseases, where they coordinate paracrine cell behavior. During regeneration, liver sinusoidal endothelial cells induce hepatocyte proliferation and angiogenesis. During fibrogenesis, they undergo morphological and functional changes, which are reflected by their role in hepatic stellate cell activation, inflammation, and distorted sinusoidal structure. Therapeutic strategies to target angiocrine signaling are in progress but are in the early stages. Here, we offer a short synthesis of recent studies on angiocrine signaling in liver homeostasis, regeneration, and fibrogenesis.

scholarly journals Angiodiversity and organotypic functions of sinusoidal endothelial cells

Angiogenesis ◽  
2021 ◽  
Author(s):  
Philipp-Sebastian Koch ◽  
Ki Hong Lee ◽  
Sergij Goerdt ◽  
Hellmut G. Augustin
Keyword(s):  
Endothelial Cells ◽  
Major Change ◽  
Fine Tuning ◽  
Liver Sinusoidal Endothelial Cells ◽  
Sinusoidal Endothelial Cells ◽  
Waste Products ◽  
Recent Advances ◽  
Organ Specific ◽  
Functional Consequences ◽  
Fenestrated Endothelium

Abstract‘Angiodiversity’ refers to the structural and functional heterogeneity of endothelial cells (EC) along the segments of the vascular tree and especially within the microvascular beds of different organs. Organotypically differentiated EC ranging from continuous, barrier-forming endothelium to discontinuous, fenestrated endothelium perform organ-specific functions such as the maintenance of the tightly sealed blood–brain barrier or the clearance of macromolecular waste products from the peripheral blood by liver EC-expressed scavenger receptors. The microvascular bed of the liver, composed of discontinuous, fenestrated liver sinusoidal endothelial cells (LSEC), is a prime example of organ-specific angiodiversity. Anatomy and development of LSEC have been extensively studied by electron microscopy as well as linage-tracing experiments. Recent advances in cell isolation and bulk transcriptomics or single-cell RNA sequencing techniques allowed the identification of distinct LSEC molecular programs and have led to the identification of LSEC subpopulations. LSEC execute homeostatic functions such as fine tuning the vascular tone, clearing noxious substances from the circulation, and modulating immunoregulatory mechanisms. In recent years, the identification and functional analysis of LSEC-derived angiocrine signals, which control liver homeostasis and disease pathogenesis in an instructive manner, marks a major change of paradigm in the understanding of liver function in health and disease. This review summarizes recent advances in the understanding of liver vascular angiodiversity and the functional consequences resulting thereof.

Liver sinusoidal endothelial cells veto CD8 T cell activation by antigen-presenting dendritic cells

2008 ◽  
Vol 38 (4) ◽  
pp. 957-967 ◽  
Author(s):  
Frank A. Schildberg ◽  
Silke I. Hegenbarth ◽  
Beatrix Schumak ◽  
Andreas Limmer ◽  
Percy A. Knolle
Keyword(s):  
Endothelial Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd8 T Cell ◽  
Liver Sinusoidal Endothelial Cells ◽  
Sinusoidal Endothelial Cells ◽  
Antigen Presenting
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