Fluorescence-labeled-hyaluronan loading test as an index of hepatic sinusoidal endothelial cell function in the rat

Hyaluronan is an endogenous glycosaminoglycan whose clearance from plasma takes place mainly in the liver sinusoidal endothelial cells. Elevated levels of serum hyaluronan have been reported in various chronic liver diseases. This phenomenon may be caused by the impaired degradation of hyaluronan in damaged liver endothelial cells and also the enhanced production in proliferated connective tissue of the liver. The aim of this investigation was to evaluate the function of uptake of the exogenously administered hyaluronan from blood in the chronically injured liver of rats. We examined plasma clearance of fluorescein amine-labeled hyaluronan and its localization and accumulation in the liver. Plasma clearance of hyaluronan became slower with severity of chronic liver injury. Fluorescence localized in sinusoids was markedly reduced and the accumulation of fluorescence in the liver tissue was significantly decreased in the cirrhotic liver compared with the control liver. These results suggest that, in chronic liver injury, the impaired clearance of hyaluronan from blood is attributed to decreased hyaluronan uptake in the liver.