Prominent Receptors of Liver Sinusoidal Endothelial Cells in Liver Homeostasis and Disease.

Ekta Pandey,Aiah S Nour,Edward N Harris

doi:10.3389/fphys.2020.00873

Abstract

Liver sinusoidal endothelial cells (LSECs) are the most abundant non-parenchymal cells lining the sinusoidal capillaries of the hepatic system. LSECs are characterized with numerous fenestrae and lack basement membrane as well as a diaphragm. These unique morphological characteristics of LSECs makes them the most permeable endothelial cells of the mammalian vasculature and aid in regulating flow of macromolecules and small lipid-based structures between sinusoidal blood and parenchymal cells. LSECs have a very high endocytic capacity aided by scavenger receptors (SR), such as SR-A, SR-B (SR-B1 and CD-36), SR-E (Lox-1 and mannose receptors), and SR-H (Stabilins). Other high-affinity receptors for mediating endocytosis include the FcγRIIb, which assist in the antibody-mediated removal of immune complexes. Complemented with intense lysosomal activity, LSECs play a vital role in the uptake and degradation of many blood borne waste macromolecules and small (<280 nm) colloids. Currently, seven Toll-like receptors have been investigated in LSECs, which are involved in the recognition and clearance of pathogen-associated molecular pattern (PAMPs) as well as damage associated molecular pattern (DAMP). Along with other SRs, LSECs play an essential role in maintaining lipid homeostasis with the low-density lipoprotein receptor-related protein-1 (LRP-1), in juxtaposition with hepatocytes. LSECs co-express two surface lectins called L-Specific Intercellular adhesion molecule-3 Grabbing Non-integrin Receptor (L-SIGN) and liver sinusoidal endothelial cell lectin (LSECtin). LSECs also express several adhesion molecules which are involved in the recruitment of leukocytes at the site of inflammation. Here, we review these cell surface receptors as well as other components expressed by LSECs and their functions in the maintenance of liver homeostasis. We further discuss receptor expression and activity and dysregulation associated with the initiation and progression of many liver diseases, such as hepatocellular carcinoma, liver fibrosis, and cirrhosis, alcoholic and non-alcoholic fatty liver diseases and pseudocapillarization with aging.

Highlights

The liver is considered a crucial organ of the body due to its involvement in numerous processes, such as metabolism, immunity, detoxification, nutrient storage, among others
Since LSECtin and L-Specific Intercellular adhesion molecule3 Grabbing Non-integrin Receptor (L-SIGN) belongs to the same C-type lectin family and share a 32% sequence identity, Li Y. et al (2009) demonstrated that the central domain of LSECtin binds with L-SIGN and along with the C terminal carbohydrate recognition domains (CRDs) domain bind with E2 glycoprotein present on Hepatitis C viron (HCV) suggesting that LSECtin binding with L-SIGN might play a role in the HCV binding to Liver sinusoidal endothelial cells (LSECs)
As the liver is bathed in portal vein blood which drains the GI tract, there are many food and bacterial antigens flowing through in which LSECs play a major role in cleaning up and tempering other immune cells within the liver

Summary

Introduction

The liver is considered a crucial organ of the body due to its involvement in numerous processes, such as metabolism, immunity, detoxification, nutrient storage, among others. They reported a reduction in the number of fenestrae, diameter and porosity in ox-LDL-treated human LSEC culture and LOX-1 siRNA resulted in reversal of these effects, suggesting its role in stress related atherogenesis (Fraser et al, 1995).

Results

Conclusion