Hepatic sinusoidal endothelial cells

I. Kosugi, H. Muro, H. Shirasawa, and I. Ito, Endocytosis of soluble IgG immune complex and its transport to lysosomes in hepatic sinusoidal endothelial cells, J. Hepatol. 76 106-114 (1992). 

Hamada, J., Cavanaugh, P.G., Miki, K., and Nicolson, G.L., A paracrine migration-stimulating factor for metastatic tumor cells secreted by mouse hepatic sinusoidal endothelial cells identification as complement component C3b. Cancer Res., 1993,53 4418-4423. 

Figure 4.1. Schematic representation of the architecture of the liver. Blood enters the liver through the portal vein (PV) and hepatic arteries (HA), flows through the sinusoids, and leaves the liver again via the central vein (CV). KC, Kupffer cells SEC, sinusoidal endothelial cells HSC, hepatic stellate cells BD, bile duct. Modified from reference 98.

Figure 4.2. Diagram outlining the pathogenesis of liver fibrosis. Injury to parenchymal cells (PC) results in the activation of Kupffer cells (KC) and sinusoidal endothelial cells (SEC) and the recruitment of inflammatory cells (IC). These cells release cytokines, growth factors and reactive oxygen species that induce activation and proliferation of hepatic stellate cells (HSC). HSCs gradually transform into myofibroblasts (MF), the major producers of extracellular matrix (ECM) proteins.

K. Kagawa, and K. Kashima, The change of sinusoidal endothelial cells in experimental liver cirrhosis—in vivo and in vitro study, Cells of Hepatic Sinusoid (D. 

J. J. Maher and R. F. McGuire, Extracellular matrix gene expression increases preferentially in rat lipocytes and sinusoidal endothelial cells during hepatic fibrosis in vivo, J. Clin. Invest. 86 1641-1688 (1990). 

S. L. Friedman and F. J. Roll, Isolation and culture of hepatic lipocytes, Kupffer cells, and sinusoidal endothelial cells by density gradient centrifugation with Strac-tan, Anal. Biochem. 767 207-218 (1987). 

Fig. 9 Possible mechanisms for cell-mediated immune responses triggered by reactive metabolites. The covalent binding of the reactive metabolite modifies hepatic proteins. The death or alteration of one hepatocyte due to mild direct toxicity may lead to the extrusion of a modified protein through the fenestrae of sinusoidal endothelial cells (SEC). The uptake of this haptenized protein by an antigen-presenting cell (APC), such as a Kupffer cell, may lead to the presentation of a metabolite-bound peptide on a major histocompatibility (MHC) class II molecule of the APC, and the recognition of this modified peptide by the T cell receptor (TCR) of a helper T cell. The latter may then provide help to a cytotoxic T lymphocyte recognizing modified peptides presented on the MHC class I molecules of hepatocytes...

Takei Y, Maruyama A, Ferdous A, Ikejima K, Enomoto N, Kitamura T, Nishimura Y, Asayama S, Nogawa M, Akaike T, Lemasters JJ, Sato N. Genetic manipulation of sinusoidal endothelial cells. Cells Hepatic Sinusoid 2001 8 142-143. 

B- and T-lymphocyte precursors, endothelial cells, hepatic sinusoids, interstitial cells of Cajal, endometrial stroma, fibroblasts... 

Kim and Rajagopalan (2010) prepared chitosan/HA multilayer scaffolds to mimic the space of Disse of liver and to preserve or enhance liver-specific behaviors of hepatocytes and liver sinusoidal endothelial cells (LSECs). Hepatocytes and LSECs cultured in the 3D hepatic model scaffold exhibited several key phenotypic characteristics for 12 days due to the enhanced heterotypic cell-cell interactions. Further, hepatocytes and LSECs on the chitosan/HA scaffolds increased CYPlAl/2 and CYP3A activity while albumin production increased threefold to sixfold. 

Figure 25-2. The formation and secretion of (A) chylomicrons by an intestinal cell and (B) very low density lipoproteins by a hepatic cell. (RER, rough endoplasmic reticulum SER, smooth endoplasmic reticulum G, Golgi apparatus N, nucleus C, chylomicrons VLDL, very low density lipoproteins E, endothelium SD, space of Disse, containing blood plasma.) Apolipoprotein B, synthesized in the RER, is incorporated into lipoproteins in the SER, the main site of synthesis of triacylglycerol. After addition of carbohydrate residues in G, they are released from the cell by reverse pinocytosis. Chylomicrons pass into the lymphatic system. VLDL are secreted into the space of Disse and then into the hepatic sinusoids through fenestrae in the endothelial lining.

Occasionally toxic compounds can directly damage the hepatic sinusoids and capillaries. One such toxic compound is monocrotaline, a naturally occurring pyrrolozidine alkaloid, found in certain plants (Heliotropium, Senecio, and Crotolaria species). Monocrotaline (Fig. 7.7) is metabolized to a reactive metabolite, which is directly cytotoxic to the sinusoidal and endothelial cells, causing damage and occlusion of the lumen. The blood flow in the liver is therefore reduced and ischemic damage to the hepatocytes ensues. Centrilobular necrosis results, and the venous return to the liver is blocked. Hence, this is known as veno-occlusive disease and results in extensive alteration in hepatic vasculature and function. Chronic exposure causes cirrhosis. 

The central event in the development of liver fibrosis is the enhanced sinusoidal deposition of extracellular matrix proteins that are mainly produced by activated HSC [86, 112, 113] and to a minor extent by endothelial cells [44-46] and hepatocytes [114, 115]. So far, no evidence has been found that KC are directly involved in the production of extracellular matrix proteins [39]. The accumulation of extracellular matrix proteins is caused by a disturbed balance between the synthesis and the degradation of the matrix proteins. This imbalance leads to a 5 to 10-fold increase in the total amount of matrix molecules and to an altered composition of the extracellular matrix. In contrast to normal livers, the sinusoids in fibrotic livers are stuffed with the fibrillar collagens type I and III. This colla-genization of the sinusoids, referred to as sinusoidal capillarization, causes severe disturbances of the blood flow and an impaired exchange of proteins between the liver cells and blood. Furthermore, this capillarization is accompanied by a loss of fenestration of the sinusoidal endothelial lining, which further hampers the diffusion of proteins between plasma and hepatic cells. 

B. Smedsrod, J. Melkko, N. Araki, H. Sano, and S. Horiuchi. Advanced glycation end products are eliminated by scavenger-receptor-mediated endocytosis in hepatic sinusoidal Kupffer and endothelial cells, Biochem. J. 322 567-573 (1997). 

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