Sinusoidal cells

Unlike the liver injury that occurs with toxic chemicals (see above), reperfusion injury affects not only the hepatocytes but also the endothelial cells that line the sinusoids as an important primary target. It is thought that there may be some aspects of preservation-reperfusion injury that are unique to the liver and UW solution is apparently more effective in this tissue than in others (Clavien aal., 1992). The principle characteristic of this injury is that it involves damage to the sinusoidal cells such that leucocytes and platelets are stimulated to adhere on reperfusion. 

Laskin, D.L. and Gardner, C.R., Role of sinusoidal cells and inflammatory macrophages in hepatotoxicity, in Drug induced Liver Disease, Kaplowitz, N. and DeLeve, L, Eds., Marcel Dekker, New York, 2002, 183-211. 

The viability and function tests described above are used to evaluate the hepatocytes within the slice. Up to now, tests to measure the viability of the non-parenchymal cells have not been reported. The presence of the latter cell types is one of the conceptual advantages of slices as compared to isolated hepatocytes. As some drug targeting devices are designed to target non-parenchymal cells in the liver, the development of tests for the sinusoidal cell types deserves more attention. For example, the uptake of substrates such as succinylated human serum albumin (Suc-HSA,which is specifically endocytosed by endothelial cells [79]), or hyaluronic acid [80], can be used to assess the functionality of endocytotic pathways in the endothelial cells in the liver [81]. Other modified proteins that are specifically taken up by Kupffer cells such as mannosylated HSA, may be used to assess the functionality of the endocytotic pathway in Kupffer cells [79]. Another parameter which can be used to assess the functionality of these non-parenchymal liver cells, is the excretion of cytokines in response to pro-inflammatory stimuli. Non-parench5mal cell function in liver slices will be described in more detail in the Section 12.7. 

Melgert et al. studied the delivery of the corticosteroid dexamethasone to fibrotic livers [240], Dexamethasone has more potent and broader anti-inflammatory effects compared with naproxen. It inhibits the release of inflammatory mediators like TNF-a, IFN-y, and IL-6 and acts as an NFkB inhibitor [241, 242], Dexamethasone coupled to albumin (Dexa-HSA) was specifically taken up by sinusoidal cells in fibrotic rat livers, whereas dexamethasone itself was mainly taken up by hepatocytes. In vivo, Dexa-HSA promoted survival in endotoxin-induced liver inflammation in rats [240], In vitro, anti-inflammatory effects of the conjugate were measured in endotoxin-challenged liver slices. Dexa-HSA inhibited the release of nitric oxide and TNF-a in a dose-dependent manner (Melgert et al. unpublished data). To further enhance the delivery to KC at present dexamethasone is coupled to manHSA, and this conjugate is studied with respect to the pharmacokinetic profile and pharmacotherapeutic effects in fibrotic rats. 

B. N. Melgert, E. Wartna, C. Lebbe, C. Albrecht, G. Molema, K. Poelstra, J. Re-ichen, and D. K. F. Meijer. Targeting of naproxen covalently linked to HSA to sinusoidal cell types of the liver, J. Drug Target 5 329-342 (1998). 

Adhesion to organ-specific structures can also be used to select metastatic variants, that will usually show increased homing to the tissue used for selection. In this way, B16 melanoma cells have been selected on lung cryostat sections (Netland and Zetter, 1981), Lewis lung carcinoma cells on hepatocyte monolayers (Brodt, 1989), and RAW117 large-cell lymphoma cells on hepatic sinusoidal cells (LaBiche et al., 1993). 

Structurally and histologically, the liver can be divided into four tissue systems (i.) intrahepatic vascular system, (2.) stroma, (3.) sinusoidal cells, and (4.) hepatocytes. 

Fig. 2.9 Liver cell and sinusoidal cells with organelles and polarized membrane compartments hepatocytes (H), sinusoids (S), Disse s space (D), erythrocytes (ER), endothelial cells (E), Kupffer cells (K), Ito cells (I), microvilli (MV), canahculus (BC), nucleolus (N), tight junctions (tj), cell nucleus (CN), mitochondria (M), smooth endoplasmic reticulum (SER), rough endoplasmic reticulum (RER), Golgi apparatus (GA), lysosomes (L), peroxisomes (P), ribosomes (R), microfilaments (ME) (modified from L. Cossel) (s. figs. 2.16-2.18)...

Although the sinusoidal cells (31 million/mg liver) make up only a relatively small proportion of the liver volume (6.3%), they constitute 30-40% of the total cell number. The total surface area of their plasma membranes is 26.5% of the total membrane surface of all liver cells. (3, 5, 23, 27, 44, 52, 56, 59) (s. figS. 2.8, 2.9)... 

Liver cells comprise the cell nucleus (= karyoplasm) and the cell body (= cytoplasm). Hepatocytes and sinusoidal cells have various types of organelles in their eosinophilic cytoplasm such as endoplasmic reticulum, Golgi apparatus, lysosomes, mitochondria, peroxisomes, ribosomes, centrioles and kinetosomes. Numerous and diverse metabolic processes take place with their help. Almost all cytoplasmic structures of liver cells are continuously renewed (up to twice daily). (20, 27, 30, 33, 35, 46-48, 50, 53, 58, 59, 69, 74) (s. figs. 2.9, 2.16-2.18) (s. tab. 2.1)... 

Bioulac-Sage, P., Lafon, M.E., Saric, J., Balabaud, C. Nerves and peri-sinusoidal cells in human liver. J. Hepatol. 1990 10 105-112... 

Jones, E.A. Hepatic sinusoidal cells new insights and controversies. Hepatology 1983 3 254-266... 

The morphological and functional integrity of the liver is vital to the health of the human organism. This essentially depends upon constant maintenance of the numerous biochemical functions of the liver and the diverse metabolic processes occurring in the hepatocytes and sinusoidal cells. 

Hepatocytes interact closely with the sinusoidal cells and Kupffer cells (e. g. in the breakdown of erythrocytes and the degradation of pyrimidine nucleotides). 

Hepatocytes and sinusoidal cells are influenced by vegetative nerve fibre endings in Disse s space. 

This cooperation not only takes place between the sinusoidal cells, but also with the hepatocytes .) endothelial and Kupffer cells complement each other through various mechanisms of endocytosis and different pathways of enzymatic clearance (2.) as a double barrier, they protect the liver cells both from toxic and undesired substances, even to the extent of self-sacrifice (i.) they intervene in the metabolism of liver cells with self-produced substances 4.) they send signal substances like cytokines (e.g. interferons) and eicosanoids (e.g. leukotrienes) to the liver cells for independent control of biochemical and biomolecular reaction cascades. 

An increase in the volume of sinusoidal cells and hepatocytes due to an enlargement of their cellular structures can be caused actively by proliferation or passively by storage processes. 

Liver cell degenerations (hydropic swelling, eosinophilic degeneration, pin cells, hyaline bodies) and cell polymorphy, single cell necrosis in the form of (acidophilic) Councilman bodies, infiltration of lymphocytes, macrophages and activated stellate cells (yet only few plasma cells and neutrophilic granulocytes), proliferation of sinusoidal cells. 

Bader A, Knop E, Kern A, Boker K, Fnihauf N, Crome O, Esselman H, Pape C, Kempka G Searing KF (1996) 3D co-culture of hepatic sinusoidal cells with primary hepatocytes - design of an organo-typical node. Exp. Cell Research, 226(1) 223-233. 

True hepatocellular carcinoma differentiation (polyclonal CEA-I-, HepPar-l-i-, sinusoidal cell CD34-f) has been described on rare occasions as a component of some adenocarcinomas from urinary bladder and stomach. Hepatoid carcinomas as components of ovarian tumors regularly express significant HepPar-1. ... 

Figure 8 The Conversion EflBciency of a 400 cpsi Square Cell Ceramic System Compared to a 400 cpsi Sinusoidal Cell Metal System.

The calculated Heat Mass Transfer Factors for 400 cpsi square and sinusoidal cell products are almost identical, even with the very much higher geometric surface area of the sinusoidal channel. The near identity of this factor... 

Analysis of a set of catalyst performance data which represent a direct comparison between the 400 cpsi square and sinusoidal cell structures indicates almost identical steady-state performance for the catalysts on the two structures. These data suggest that the Heat Mass Transfer Factor can in fact be used to predict relative catalyst performance when other aspects of the experiment such as washcoat loading, substrate volume, and test conditions are held constant. 

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