Differentiation in hepatic and splenic phagocytic activity during reticuloendothelial blockade with cholesterol-free...

We have shown earlier that liver and spleen reticuloendothelial cells have low affinity to phagocyte liposomes containing cholesterol. In the present study, we predosed mice with cholesterol-rich (identical to = 46.6 mol% cholesterol content) and cholesterol-free (identical to 0 mol%) liposomes to saturate the reticuloendothelial cells and examined the tissue distribution of the second dose of the test liposomes containing an aqueous marker, 125I-labelled poly(vinylpyrrolidone). The result shows that both preparations of the predosed liposomes caused suppression in hepatic uptake and delay in the blood clearance of the test liposomes, but the cholesterol-free liposomes were more effective in producing these effects than the cholesterol-rich liposomes. The suppression in hepatic phagocytic function, in accordance with the 'spillover' phenomenon [16, 17], caused an enhancement in spleen and lung uptake. The increase in lung uptake was proportionally related to the degree of suppression in the hepatic uptake, but the results of the splenic uptake showed some discrepancy. The predosed cholesterol-free liposomes which caused the maximum spillover of the test liposomes from the liver did not achieve maximum enhancement in the splenic uptake. Instead, the maximum enhancement was recorded with the predosed cholesterol-rich liposomes. This discrepancy in splenic uptake suggests that the predosed liposomes caused saturation of not only liver also the spleen reticuloendothelial system. However, instead of suppression in the splenic uptake due to the saturation, enhancement in uptake of the test liposomes was observed. We suggest the cause of this apparent increase the splenic phagocytic activity may be due to stimulation, by some unknown mechanism of splenic macrophages endothelial cells and/or lymphocytes, to phagocyte the excess of the test liposomes spillover from the liver with impaired phagocytic function.