No abstract

Very low density lipoproteins, newly secreted by cultured rat hepatocytes into a serum-free medium, contain some cholesteryl esters although the percentage of total cholesterol in ester form is less than that in plasma very low density lipoproteins. When acyl CoA:cholesterol acyltransferase activity in hepatocytes was stimulated by the addition of 25-hydroxycholestero1 (10 pg/ml) or mevalonolactone (1 mM), the absolute amount of esterified cholesterol secreted in very low density lipoproteins increased significantly, but the amount of free cholesterol decreased or showed no change. Thus the percentage of very low density lipoprotein cholesterol in ester form increased, in some experiments to as much as 50% of the total. These results provide additional evidence that hepatic acyl CoA:cholesterol acyltransferase plays a role in the generation of some of the cholesteryl ester in newlysecreted lipoproteins. They further suggest that changes in the activity of the enzyme can potentially regulate the fraction of cholesterol secreted in esterified form.-Drevon, C. A., S. C. Engelhorn, and D. Steinberg. Secretion of very low density lipoproteins enriched in cholesteryl esters by cultured rat hepatocytes during stimulation of intracellular cholesterol esterification. J . Lipid Res. 1980. 21: 1065-107 1.Supplementary key words acy1CoA:cholesterol acyltransferase . 1ecithin:cholesterol acyltransferase . 25-hydroxycholesterol . mevalonolactone Much of the cholesteryl ester moiety in plasma lipoprotein fractions is probably formed within the plasma through the action of 1ecithin:cholesterol acyltransferase (LCAT) (1). In patients with an inherited LCAT deficiency, only 5-17% of total plasma cholesterol is present as cholesteryl ester (1) compared to about 75% in normal subjects. Almost all the cholesteryl ester in the plasma of these patients can be recovered in the very low density lipoprotein (VLDL) fraction (2). Since there is no measurable LCAT activity in the plasma of these patients, there must be alternative sources of this plasma VLDL cholesteryl ester, including secretion by liver andlor intestine of VLDL (or VLDL precursors) already containing cholesteryl esters. It has been previously demonstrated that VLDL isolated from the Golgi apparatus in rat liver contains some cholesteryl ester (3), and that nascent lipoproteins secreted by perfused rat liver (4-7) and cultured rat hepatocytes (8) also contain a significant amount of cholesteryl ester.When guinea pigs (9-11) or rats (12) are given dietary supplements of cholesterol, there is an increase in acy1CoA:cholesterol acyltransferase (ACAT) activity in microsomes of intestinal mucosal cells and an increase in the amount of cholesteryl ester in the triglyceride-rich lipoproteins of' intestinal lymph. Since LCAT activity in intestinal lymph is very low (10, 13), these data suggest that intracellular ACAT may play a role in the production of cholesteryl esters for incorporation into intestinal VLDL prior to its secretion. ACAT activity in cultured rat hepatocytes can be...

No abstract

No abstract

The effect of IL-4 on the IFN-gamma-induced state of activation of cultured human monocytes was investigated with regard to their ability to produce hydrogen peroxide and their antileishmanial capacity towards the intracellular parasite Leishmania donovani. IL-4 was found to inhibit the IFN-gamma-dependent hydrogen peroxide production of monocytes. Treatment of monocytes with IFN-gamma (200 to 600 U/ml) for 48 h increased the hydrogen peroxide production fourfold above background. Coincubation of the monocytes with IL-4 (1 to 1000 U/ml) and IFN-gamma (200 to 600 U/ml) inhibited this increase by 50 to 100%. IL-4 alone did not modulate the hydrogen peroxide production of monocytes. Pretreatment of monocytes with IL-4 for 20 min to 3 h was already effective in preventing the IFN-gamma response. Addition of IL-4 not later than 6 h after the start of incubation with IFN-gamma was necessary for an optimal inhibitory effect. IL-4 also inhibited the IFN-gamma-induced antileishmanial capacity of monocytes: IFN-gamma (1000 U/ml) induced a 54 +/- 10% reduction in the number of parasites. Monocytes treated with combinations of IL-4 (100 to 1000 U/ml) and IFN-gamma (1000 U/ml) were unable to reduce the parasite numbers. IL-4 alone did not alter the uptake of Leishmania donovani nor induce antileishmanial activity. These results demonstrate that IL-4 disables human cultured monocytes to respond to IFN-gamma activation.

No abstract

No abstract

No abstract