REGULATION OF CHOLESTEROL-SYNTHESIS AND ESTERIFICATION IN PRIMARY CULTURES OF MACROPHAGES FOLLOWING UPTAKE OF CHYLOMICRON REMNANTS

The effects of chylomicron remnants (CR), beta-very-low-density-lipopr oteins (beta-VLDL) and low-density-lipoproteins (LDL) on intracellular cholesterol synthesis and esterification in primary rabbit macrophage s was determined by assaying for HMG-CoA reductase activity and choles terol esterification. At physiological cholesterol concentrations, bot h CR and LDL inhibited cholesterol synthesis by almost 60% while beta- VLDL was less potent achieving only 30% inhibition. Cholesterol esteri fication rates were increased four-fold by CR and LDL, whereas beta-VL DL increased esterification 14 times above controls. Qualitatively, th e effect of CR on cholesterol synthesis and esterification in rabbit m acrophages differs from observations in transformed macrophage cells. Quantitatively, the enhanced rates of cholesterol esterification and w eak inhibition of cholesterol synthesis following beta-VLDL uptake may explain why this lipoprotein rapidly induces foam cell formation in v itro.