Hepatic sinusoids: What are they? Sinusoidal Endothelial Cells and Liver Cells

Bile ductules are derived from the canalicular regions of the hepatocytes, and the bile in these ducts flows against the blood flow through the sinusoid.

This ensures that, under normal circumstances, the two physiologically distinct fluids are kept separate from each other.

These sinusoids run between the portal triads, consisting of a terminal portal vein and a terminal hepatic arteriole (along with a bile duct) through hepatocyte cords separated from the sinusoid by the sinusoidal endothelial cells, the peri-sinusoidal space, or dissection space, to a central venule.

The hepatic sinusoid is a unique vascular structure with highly specialized endothelial cells and phagocytic Kupffer cells that clear the blood.

Although highly porous compared to capillaries elsewhere in the body, it provides a selective barrier for significant substances such as chylomicrons while allowing rapid exchange of smaller materials between the blood and liver parenchyma cells, such as remnants rich in cholesterol.

Kupffer cells play an essential role in the host’s defense through their phagocytic and secretory functions.

Many of these posts are probably involved in regulating the sinusoidal blood flow, endothelial cell function including porosity, some aspects of the metabolism of the liver parenchymal cells, and controlling fat storage and functions of cells pit.


The star cell is positioned as a pericyte, which, in addition to its role as a vitamin A storage site, is also contractile and may be the primary cell involved in regulating sinusoidal diameter and blood flow.

All these cell types are uniquely specialized in structure and function to form exchange vessels that meet the unique needs of the parenchymal tissue surrounding the sinusoids.

Sinusoidal endothelial cells

The sinusoidal endothelial cells form the fenestrated lining of the hepatic sinusoids and constitutively express the TLR4 and CD14 proteins and TLR9.

In addition, messenger RNA (mRNA) for TLR1 proteins up to TLR9 is expressed in sinusoidal endothelial cells, and the functional expression of TLR3 (Toll-like receptor three genes) has been demonstrated by the ability of poly (I: C) sinusoidal cells to reduce the replication of the hepatitis B virus in immortalized hepatocytes.

After exposure to lipopolysaccharides, the sinusoidal endothelial cells showed reduced activation of nuclear factor NF-κB, expression of CD54 (Cluster of Differentiation 54), and a reduced ability to promote leukocyte adhesion.

In sinusoidal endothelial cells, tolerance to lipopolysaccharides is not regulated at the level of surface expression of the TLR4 protein but seems to be related to prostanoid expression.

The role of sinusoidal endothelial cells in the hepatic uptake of lipopolysaccharides is currently unclear.

In normal liver, sinusoidal endothelial cells (LSEC) are characterized by specific characteristics that include the presence of fenestra and high endocytic activity.

The vascular endothelial growth factor (VEGF for its acronym in English) released by hepatocytes and HSCs plays a vital role in maintaining this differentiated phenotype through the pathways independent and dependent on nitric oxide (NO for its acronym in English ).

Chronic hepatic injury is associated with an early loss of cellular fenestration (i.e., capillarization of the sinusoids) that precedes the onset of fibrosis. Activated endothelial cells produce TGF-β, PDGF-BB, and collagen I, which contribute to the activation of hepatic stellate cells.

In contrast, a recent study has shown that restoring the differentiation of hepatic sinusoidal endothelial cells can accelerate the regression of fibrosis by promoting the quiescence of hepatic stellate cells.

In fact, in vitro experiments indicate differentiated hepatic sinusoidal endothelial cells promote the reversal of activated hepatic stellate cells in an inactive phenotype by paracrine interactions, as shown in coculture studies.

The in vivo relevance of these findings has been explored in rats with thioacetamide-induced cirrhosis.

Early restoration of the phenotype of normal hepatic sinusoidal endothelial cells is induced by a 7-day cycle with a soluble guanylate cyclase activator (sGC) without altering the density of the activated phenotype and the level of fibrosis.

After the interruption of the soluble guanylate cyclase, the differentiated hepatic sinusoidal endothelial cells promote the subsequent reversion of activated hepatic stellate cells to inactivity and accelerate the recovery of fibrosis.

Currently unknown whether hepatic stellate cells revert to a so-called reversed phenotype or a physiological (i.e., quiescent) phenotype.

Interestingly, a recent study identifies an additional impact of vascular endothelial growth factor on the regression of fibrosis.

In fact, in a bile duct ligation recovery model, vascular endothelial growth factor promotes the adhesion of monocyte-endothelial cells and restores sinusoidal permeability.

Allowing the infiltration of monocytes, the accumulation of ” restorative macrophages” in the scar tissue, and the up-regulation of MMP13 to reshape the scar.

These data indicate that differentiated hepatic sinusoidal endothelial cells play a guardian role in regulating both fibrogenesis and fibrinolysis.

Hepatic sinusoidal endothelial cells

Hepatic sinusoidal endothelial cells are highly specialized cells that coat hepatic sinusoids. The sinusoidal hepatic endothelial cells are distinguished by the presence of fenestrations in their cell membranes.

It is believed that fenestrations facilitate the selective passage of antigens between the sinusoid and the liver parenchyma and may also increase the surface area available for antigen presentation.

This strategic location places the sinusoidal hepatic endothelial cells in the ideal position to interact with the antigens and immune cells that pass between the liver and the portal venous system.

Several studies have shown that, in addition to serving as a structural component of hepatic sinusoids, hepatic sinusoidal endothelial cells are immune cells with the ability to capture and present antigens to T cells.

As with Kupffer cells, there is considerable controversy surrounding the immunological function of hepatic sinusoidal endothelial cells.

Although hepatic sinusoidal endothelial cells can capture various antigens in vivo and in vitro, they cannot activate T cells in the absence of exogenous costimulation.

The differences in the results can be derived from the use of more specific cell isolation methods in this latter study.

The discovery that hepatic sinusoidal endothelial cells are not capable of independently triggering an immune response mediated by T cells does not exclude.

However, the possibility that hepatic sinusoidal endothelial cells, together with dendritic cells or Kupffer cells, play an important role in antigen presentation in the liver.