Recent animal studies show that endothelial cells in liver sinusoids are the main site for removal of sodium hyaluronate from the circulation. Few data with respect to hyaluronate metabolism are available in man. Serum hyaluronate levels were measured in 119 patients with liver disease by a sensitive assay. The hyaluronate level was significantly increased in liver cirrhosis, in comparison with healthy controls and with patients with noncirrhotic liver disease. The results suggest a role for the human liver in elimination of hyaluronate from circulation. Quantification of serum hyaluronate may be a useful test of liver endothelial cell function.
Recent interest has focused on the morphology and function of liver sinusoidal cells (1). The three most common types of sinusoidal cells are endothelial cells (LEC), Kupffer cells and fat-storing cells. Both LEC and Kupffer cells are part of the reticuloendothelial system; Kupffer cells phagocytize particulate material, and LEC endocytose fluid at a high rate. Sodium hyaluronate (or hyaluronic acid) is a high molecular weight polysaccharide which is widely distributed in connective tissues and produced mainly by mesenchymal cells and enters the blood via the lymph (2).
During studies of the metabolism of sodium hyaluronate in rabbit, rat and mouse (3-5), the polysaccharide was rapidly taken up from the blood by the liver and was accumulated in the nonparenchymal cell fraction ( 3 , 4). In vitro studies on purified cell populations from rat liver show that LEC specifically and rapidly accumulated and degraded hyaluronate (6). Neither hepatocytes nor Kupffer cells have this activity (6, 7). Recent electron microscopic autoradiographic studies confirm that radioactive hyaluronate injected intravenoulsy in the rat is accumulated by the liver exclusively in LEC (Fraser, J. R. E. et al., unpublished data).
Trace amounts of radioactive hyaluronate injected intravenously in man have a half-live in serum of 2.5 to 5.5 min ( 8 ) , i.e., the same as in rabbits (2). The polysaccharide is rapidly degraded to low molecular weight ma-