Hepatic sinusoidal endothelium

Carretero, J., Obrador, E., Esteve, J.M., Ortega, A., Pellicer, J.A., Sempere, F.V., and Estrela, J.M. (2001). Tumoricidal activity of endothelial cells. Inhibition of endothelial nitric oxide production abrogates tumor cytotoxicity induced by hepatic sinusoidal endothelium in response to B16 melanoma adhesion in vitro. J. Biol. Chem. 276(28), 25775-25782. 

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.

Kishi et al. (169)evaluated the acute toxicity of Lipiodol infusion into the hepatic arteries (HAD of beagles and found the influence of Lipiodol HAI to be dose dependent. The infused Lipiodol first passed through an arterioportal communication and distributed through the hepatic sinusoids to pulmonary capillaries and thence into systemic blood circulation. The circulation and embolization of oil droplets were found in the renal tubular cells of supracapsular cortex, the choroid plexus, the vascular endothelium, and the pancreatic duct epithelium, showing a process of intracellular collection of Lipiodol from the systemic blood circulation and of further metabolism-provoking cellular reactions. 

Electron microscopic studies have shown that in the liver of the rat the sinusoids are lined by a discontinuous endothelium. The cells have no well defined basement membrane and may be separated from each other by gaps of several thousand Angstrom units. When particles of smaller diameter than these gaps are introduced into the circulation they can enter the subendothelial space of Disse and come into direct contact with the microvilli on the surface of the hepatic parenchymal cells (Bennet et al. 1959). Following the intravenous injection of chyle, chylomicrons could be seen within the lumen of hepatic sinusoids, within gaps of their endothelial lining and within the subendothelial space (French 1963). 

Anasagasti, M.J., Alvarez, A., Martin, J.J., Mendoza, L., and Vidal-Vanaclocha, F. (1997a). Sinusoidal endothelium release of hydrogen peroxide enhances very late antigen-4-mediated melanoma cell adherence and tumor cytotoxicity during interleukin-1 promotion of hepatic melanoma metastasis in mice. Hepatology 25(4), 840-846. 

The passage of most foreign compounds from the blood into the liver normally is not restricted because the endothelium of the hepatic blood sinusoids behaves as a porous membrane. Hence, drugs with molecular weights lower than those of most protein molecules readily reach the hepatic extracellular fluid from the plasma. A number of compounds are taken up into the liver by carrier-mediated systems, while more lipophilic... 

The size of the VLDL particle in plasma diminishes and its density increases as triglyceride is hydrolyzed by endothelial lipoprotein lipase, and the particles are thus converted to intermediate-density lipoproteins (IDL) (B32, S35). The IDL detach from the endothelium, and some are taken up by hepatic B-100, E receptors. The remaining particles in the circulation are further depleted of some cholesteryl ester (by an unknown mechanism), and most of the remaining triglyceride (probably by hepatic triglyceride lipase, in the liver sinusoids) (D5). Hie resulting LDL particles are largely composed of cholesteryl ester as the core lipid and apoB-100 as the apolipoprotein. 

Hepatic stellate cells (HSC) are star-shaped cells with long cytoplasmic extrusions. They were first described over 150 years ago hy von Kupffer, but for many years their function remained a mystery. They are found in the space of Disse adjacent to the overlying endothelium and hepato-cytes, and in the normal liver they represent 5-8% of all liver cells. Under resting conditions HSC store retinoids in numerous vitamin A-rich lipid droplets and are thought to regulate sinusoidal blood flow via contractile intracellular filaments. HSC are the principal cells involved in liver fibrosis, remodelling extracellular matrix and synthesising scar tissue in response to liver injury. 

In the simplest analysis, a compound which is excreted in the bile has to pass from the plasma into the liver cells and then into the bile canaliculi. First the compound has to cross from the plasma to the extracellular fluid of the liver. According to Schanker (1962b), the endothelium of the blood sinusoids is a very permeable membrane and all molecules whose size is less than that of protein molecules readily equilibrate between plasma and the extracellular fluid of the liver. The compound then has to enter the liver cell and for substances which are secreted into bile in a higher concentration than in plasma, there appears to be a specialized process for their uptake by the cell (see Section III, B, 6, and Schanker, 1968). A further transport mechanism seems to be involved in the transfer of secreted substances from hepatic cell to bile. Thus, there are at least three membranes which such compounds have to cross in their passage from plasma to bile. The first seems ver> porous, but the latter two ap-... 

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