STRUCTURE AND FUNCTION OF SINUSOIDAL LINING CELLS IN THE LIVER

The hepatic sinusoid harbors 4 different cells: endothelial cells (100 , 101), Kupffer cells (96, 102, 103), fat-storing cells (34, 51, 93), and pit cells (14, 107, 108). Each cell type has its own specific morp hology and functions, and no transitional stages exist between the cel ls. These cells have the potential to proliferate locally, either in n ormal or in special conditions, that is, experiments or disease. Sinus oidal cells form a functional unit together with the parenchymal cells . Isolation protocols exist for all sinusoidal cells. Endothelial cell s filter the fluids, exchanged between the sinusoid and the space of D isse through fenestrae (100), which measure 175 nm in diameter and are grouped in sieve plates. Fenestrae occupy 6-8% of the surface (106). No intact basal lamina is present under these cells (100). Various fac tors change the number and diameter of fenestrae [pressure, alcohol, s erotonin, and nicotin; for a review, see Fraser et al (32)]. These cha nges mainly affect the passage of lipoproteins, which contain choleste rol and vitamin A among other components. Fat-storing cells are pericy tes, located in the space of Disse, with long, contractile processes, which probably influence liver (sinusoidal) blood flow. Fat-storing ce lls possess characteristic fat droplets, which contain a large part of the body's depot of vitamin A (91, 93). These cells play a major role in the synthesis of extracellular matrix (ECM) (34, 39-41). Strongly reduced levels of vitamin A occur in alcoholic livers developing fibro sis (56). Vitamin A deficiency transforms fat-storing cells into myofi broblast-like cells with enhanced ECM production (38). Kupffer cells a ccumulate in periportal areas. They specifically endocytose endotoxin (70), which activates these macrophages. Lipopolysaccharide, together with interferon gamma, belongs to the most potent activators of Kupffe r cells (28). As a result of activation, these cells secrete oxygen ra dicals, tumor necrosis factor, interleukin 1, interleukin 6, and a ser ies of eicosanoids (28) and become cytotoxic against tumor cells [e.g. , colon carcinoma cells (19, 22, 48)]. Toxic secretory products can ca use necrosis of the liver parenchyma, which constitutes a crucial fact or in liver transplantation (55). Pit cells possess characteristic azu rophylic granules and display a high level of spontaneous cytolytic ac tivity against various tumor cells, identifying themselves as natural killer cells (10). The number and cytotoxicity of pit cells can be con siderably enhanced with biological response modifiers, such as Zymosan or interleukin 2 (8). Pit cell proliferation occurs within the liver, but recent evidence indicates that blood large granular lymphocytes d evelop into pit cells in 2 steps involving high- and low-density pit c ells (88). Kupffer cells control the motility, adherence, viability, a nd cytotoxicity of pit cells (89), whereas cytotoxicity against tumor cells is synergistically enhanced (80, 81).