Lipid synthesis in macrophages derived from the human cell line THP-1: modulation of the effects of native and oxidized chylomicron-remnant-like particles by oestrogen

The effects of native and oxidized chylomicron remnants on the synthesis of cholesteryl ester and triacylglycerol in macrophages, and the way that thi s is influenced by exposure of the cells to oestrogen, was investigated usi ng the human monocyte cell line THP-I and chylomicron-remnant-like particle s containing human apolipoprotein E (CRLPs). Synthesis of the lipids was me asured by the incorporation of [H-3]oleate into cholesteryl ester and triac ylglycerol. CRI-Ps (5-40 mug of cholesterol/ml) containing either trilinole in or triolein as the triacylglycerol component caused a dose-dependent dec rease in cholesteryl ester formation, while triacylglycerol production was unchanged. After oxidation of the CRI-Ps, the level of thiobarbituric acid- reactive substances was increased by 6.3-fold and 2.2-fold in particles con taining trilinolein and triolein respectively. Furthermore, CRI-Ps containi ng oxidized trilinolein lost their ability to down-regulate cholesterol est erification, while CRLPs containing oxidized triolein did not. Both types o f oxidized CRLPs decreased triacylglycerol synthesis. Treatment of the macr ophages with 17 beta -oestradiol caused increases of approx. 94% and 34% in the synthesis of cholesteryl ester and triacylglycerol respectively in the absence of CRLPs. The differences between control and oestrogen-treated ce l Is were abolished, however, when CRLPs (40 mug of cholesterol/ml) were ad ded to the incubations. In addition, in contrast with their lack of effect in control cells, CRLPs containing oxidized trilinolein decreased cholester ol esterification in oestrogen-treated cells by approx. 48%. These findings with CRLPs suggest that chylomicron remnants have significant effects on c holesteryl ester and triacylglycerol synthesis in macrophages, which may be modulated both by the oxidation state of the particles and by oestrogen.