Vitamin Kupffer cells

Vitamin A is assumed to be contained mainly in the Kupffer cells of the liver. The intracellular distribution of the vitamin has also been studied in chicken liver. Twenty-one per cent of the vitamin is found in the nucleus, 7% in the mitochondria, and 72% in the supernatant. Therefore, the vitamin seems to be concentrated essentially in the supernatant fluid, and the amount of vitamin associated with the nucleus and the mitochondria is probably due to contamination of the fraction by the supernatant vitamin A. This intracellular distribution might be peculiar to the liver— the main site of vitamin A storage therefore, the cellular distribution of the vitamin gives no clue as to its mode of action. The liver vitamin is bound to protein. The protein that is bound to the alcohol derivative of vitamin A is probably different from that bound to the ester derivative of vitamin A. 

A number of investigators have explored the potential roles of the nonparenchymal cells in the storage and metabolism of vitamin A in the liver. It has been shown convincingly that the Kupffer cells do not play an important role in the storage of vitamin A in the liver under normal conditions. Thus, when Kupffer cells were isolated from livers of rats on normal or on excess vitamin A-containing diets, the content of vitamin A in the Kupffer cells was found to be substantially less than that in hepatocytes (expressed on a per cell or per milligram DNA basis) (Linder et al., 1971 Hori and Kutamura, 1972 Peterson et aL, 1973). 

Vitamin A demonstrated in the liver and the adrenal gland of the rat by fluorescence method. A. Liver of a rat deficient in vitamin A. No fluorescence. B. Liver of a normal rat. Moderate amounts of vitamin A fluorescence are present in the Kupffer cells and at places in fine droplets at edges of liver cells. C. Liver of a rat made hyper-vitaminotic with vitamin A. Marked vitamin A fluorescence is seen in the Kupffer cells which have apparently proliferated. Moderate amounts of fluorescence in small lipoid droplets within the liver cells. />. Adrenal of a vitamin A-deficient rat. No fluorescence. E. Adrenal of a well-fed rat. Moderate amounts of vitamin A fluorescence are seen in the lipoid droplets of the zona fasciculata. F. Adrenal of a rat made hypervitaminotic with vitamin A. There is striking vitamin A fluorescence of the lipoid droplets of the fascicular layer. The lipoid droplets of the zona glomerulosa are free of vitamin A fluorescence. 

Vitamin A is stored chiefly in the liver, the median level in normal subjects being 320 I.U. per gram of liver, according to Moore (Chapter 8). Glover and Morton have suggested that vitamin A may be stored in two sites in the liver, the Kupffer cells and the true storage cells, and that... 

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. 

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