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FIGURE 1. Structure of hepatic lobule. Hepatic cords of the lobule consist of PCs. ECs form the thin lining of the sinusoids (S). Kupffer cells (KC) are tissue macrophages and belong to the monocyte-macrophage cell lineage. Stellate cells (HSC) lie in the space between PCs and ECs, and store 80% of vitamin A of the whole body as retinyl palmitate in the lipid droplets in the cytoplasm.

FIGURE 1. Structure of hepatic lobule. Hepatic cords of the lobule consist of PCs. ECs form the thin lining of the sinusoids (S). Kupffer cells (KC) are tissue macrophages and belong to the monocyte-macrophage cell lineage. Stellate cells (HSC) lie in the space between PCs and ECs, and store 80% of vitamin A of the whole body as retinyl palmitate in the lipid droplets in the cytoplasm.

Sato et al., 2003; Senoo, 2004; Senoo etal., 1997; Wake, 1971,1980) that lie in the space between SECs and PCs are considered to be derived from mesenchymal origin. Both ECs and SCs are derived from mesenchymal tissue, namely, septum transversum. Kupffer cells are from monocyte-macrophage system. SCs that store vitamin A in their cytoplasm have been found in extrahe-patic organs (kidney, intestine, lung, pancreas, and so on) and characterized (Matano et al., 1999; Nagy et al., 1997; Wake, 1980). The purpose of this chapter is to survey recent progress in studies of structure and function of the HSCs (vitamin A-storing cells).

II. MORPHOLOGY OF HSCs

HSCs [Fig. 1; fine structure of the HSCs is thoroughly described in the review of Wake (1980)] distribute regularly within hepatic lobules. The cell consists of a spindle-shaped or angular cell body and long and branching cytoplasmic processes which encompass the endothelial tubes of sinusoids (Wake, 1995, 1998). Some processes penetrate the hepatic cell plates (platelike structures formed by hepatic PCs) to reach the neighboring sinusoids to taper off to several subendothelial processes. Accordingly, a single SC wraps two or three, sometimes four, sinusoids with long processes. The total length of sinusoids surrounded by a single SC is 60-140 mm in the rat liver.

The subendothelial processes of the SCs are flat and have three cell surfaces; inner, outer, and lateral. The inner one is smooth and adheres to the adluminal (basal) surface of ECs. Between the two cells, namely between ECs and SCs, the basement membrane components such as type IV collagen and laminin are intercalated. The outer surface, facing to the perisinusoidal space (space of Disse), is decorated with short microvillous protrusions. The lateral edges of the subendothelial processes are characteristically studded with numerous spikelike microprojections whose tips make contacts with the microvillous facets of the hepatic PCs. The SCs adhere to ECs through basement membrane components, and, on the other hand, make spotty contacts with PCs.

The HSCs have been demonstrated at molecular and morphological levels to adhere each other by adherens junctions (Hiagashi et al., 2004) and gap junctions (Greenwel et al., 1993).

III. REGULATION OF VITAMIN A HOMEOSTASIS BY HSCs

Vitamin A (Fig. 2) is known to regulate diverse cellular activities such as cell proliferation, differentiation, morphogenesis, and tumorigenesis (Blomhoff, 1994; Chawla et al., 2001). In physiological conditions, HSCs store 80% of the total vitamin A in the whole body as retinyl palmitate in lipid droplets in the cytoplasm, and regulate both transport and storage of vitamin A.

The concentration of vitamin A in the bloodstream is regulated within the physiological range by these HSCs. By receptor-mediated endocytosis, the cells take up retinol from the blood, where it circulates as a complex of retinol and a specific binding protein called retinol-binding protein (RBP) (Blomhoff, 1994) (Fig. 3). Once inside the cell, free retinol has several fates, one of which is reformation of the complex with RBP and returns to the bloodstream (Blomhoff, 1992a,b,c; Senoo, 2000). Thus, the HSCs are important for the regulation of homeostasis of vitamin A.

When [3H]retinol was injected via portal vein, the largest amount of the labeled retinol was taken up by the liver within 90 min after injection, although the labeled material was detected in all organs examined (Senoo et al., 1984). The radioactivity of the retinol in the liver did not change until

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