Bile ductulites 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, which consists 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 and the peri-sinusoidal space, or dissection space, to a central venule.
Although highly porous compared to capillaries elsewhere in the body, it provides a selective barrier for large 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 important role in the defense of the host through its phagocytic and a multitude of secretory functions.
Many of these posts are probably involved in regulating the sinusoidal blood flow, endothelial cell function including porosity, some aspects of metabolism of the liver parenchymal cells and regulating 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 main cell involved in the regulation of sinusoidal diameter and blood flow.
All these cell types are uniquely specialized in structure and function to form exchange vessels that meet the special 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 as well as 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 3 gene) 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 key role in the maintenance of 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 (ie, capillarization of the sinusoids) that precedes the onset of fibrosis. Activated endothelial cells produce TGF-β, PDGF-BB and collagen I, which contributes 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 that 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.
Whether hepatic stellate cells revert to a so-called reversed phenotype or a physiological (ie, quiescent) phenotype is currently unknown.
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.
Taken together, these data indicate that differentiated hepatic sinusoidal endothelial cells play a guardian role in the regulation of both fibrogenesis and fibrolysis.
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 are very capable of capturing various antigens in vivo and in vitro, they lack the ability to activate T cells in the absence of exogenous costimulation.
The differences in the results can be derived from the use of more specific methods of cell isolation 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.