Age–Related Changes in the Endocytic Capacity of Rat Liver Kupffer and Endothelial Cells

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Abstract
There are many indications that the functional capacity of the reticuloendothelial system (RES) declines with age. The aim of this study was to investigate the cellular basis of age–related changes in the clearance function of the RES. The experiments were focused mainly on Kupffer and endothelial cells of the liver which represent a major part of the RES and are primarily responsible for clearance of colloidal material from the circulation. The clearance capacity of the RES was tested clinically and experimentally by intravenous injection of colloids, such as radiolabeled heataggregated colloidal albumin. Age–related changes in the endocytosis of 125I–labeled colloidal albumin (CA) in rats were determined by clearance and organ distribution of different doses of intravenously injected CA, uptake of CA by Kupffer and endothelial liver cells in vivo as determined after isolation of the cells from injected rats and kinetic studies on CA uptake by Kupffer cells in culture. The results show that, at a low dose, the clearance of CA is primarily determined by liver blood flow. At a higher saturating dose, plasma clearance and uptake by the liver are not significantly decreased with age. Endocytosis by endothelial cells, which accounts for about 60% of that of the whole liver, is also unchanged with age. In contrast, a significant decrease in endocytic capacity was observed for Kupffer cells in vivo. This age–related functional decline was also observed in Kupffer cells which were isolated from rats of different ages and maintained in culture. It is concluded that the overall capacity of the liver to clear the circulation of colloidal material is not necessarily affected by age. However, the Kupffer cell–specific decrease in endocytic capacity with advancing age may be important in the increased sensitivity to agents which are exclusively removed by Kupffer cells.