14C-labelled cholesterol injected intraperitoneally into rats was shown to be taken up by the reticulo-endothelial cells of the sternal lymph nodes and partly converted into 14C-labelled cholesteryl ester. The specific activity of the 14C_ labelled cholesterol in the nodes fell rapidly, while that of the 14C-labelled cholesteryl ester formed remained relatively high, suggesting that esterification of the cholesterol and its fixation as cholesteryl ester was brought about by reticulo-endothelial cells. It was also shown that 14C-labelled cholesterol was taken up by rabbit macrophages in vitro and partly esterified in these cells. The significance of the findings in relation to the pathogenesis of atheroma is discussed.
The uptake and metabolism of "4C-labelled triglyceride by R.E. cells in rat lymph nodes has been investigated. After the intraperitoneal injection of a corn oil emulsion containing glyceryl tripalmitate-1-14C uptake of labelled triglyceride by the R.E. cells in the nodes occurs. The uptake is accompanied by hydrolysis of the triglyceride and reincorporation of the liberated fatty acid mainly into phospholipid. Where cholesterol suspension is injected together with the triglyceride emulsion the 14C-labelled fatty acid is also incorporated into cholesterol ester in the nodes. Investigation by gas-liquid chromatography of the labelled fatty acid in each of the lipid moieties in the nodes showed that some chain elongation of the 14C-labelled palmitic acid occurred, but that the stearic acid formed appeared only in the phospholipid fraction.
The metabolism of cholesterol ester by the reticulo-endothelial cells in the sternal lymph nodes of rats was studied over a time period of 7 days. After the intraperitoneal injection of cholesterol-3H oleate-1-14C the uptake of ester by the RE cells in the nodes was shown to be accompanied by its partial hydrolysis. A progressive rise in the 3H/'4C ratio of the node lipid extract showed that the turnover of the labelled oleate and its removal from the nodes was more rapid than that of the labelled cholesterol. In addition the fatty acid of the cholesterol ester was found to be incorporated into other lipid moieties in the nodes, particularly into phospholipid. Of this, lecithin and, to a lesser extent, sphingomyelin and cephalin were labelled.OBSERVATIONS concerning the metabolism of cholesterol and cholesterol ester by reticulo-endothelial cells are of interest not only because they add to our understanding of the lipid metabolism of these cells but also because they may provide information about the role of reticulo-endothelial cells in the tissues both in physiological and in pathological conditions [Byers et al., 1957;Diluzio, 1960;. Such knowledge may provide information about the part played by these cells in the accumulation and removal of cholesterol from the tissues, including the atheromatous arterial wall, in which reticulo-endothelial cells containing cholesterol are present.When esterified cholesterol is ingested by reticulo-endothelial cells it is less readily removed than free cholesterol; cholesterol oleate has been shown to remain in the cells for more than 18 months [Day and French, 1961]. Nevertheless, the uptake of esterified cholesterol does evoke a metabolic response from RE cells, for the cholesterol ester becomes partially hydrolyzed [Day and French, 1959; and its uptake also results in the accumulation of phospholipid within the cells [Day, 1960 a]. The cells not only hydrolyze esterified cholesterol but also esterify the free form [Day and French, 1959;Day and Gould-Hurst, 1961] and synthesize phospholipid in response to free cholesterol uptake [Day, 1962;Day and Fidge, 1965]. Reticulo-endothelial cells are not able to oxidize the side chain of cholesterol [Day, 1961] but they appear to facilitate the incorporation of cholesterol into lipoprotein which probably assists in its suspension and dispersion [Day et al., 1964 b].In the present work the metabolism of cholesterol ester by reticuloendothelial cells has been further studied using either double-labelled
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