ESSENTIAL DIFFERENCES IN CHOLESTERYL ESTER METABOLISM BETWEEN HUMAN MONOCYTE-DERIVED AND J774 MACROPHAGES - EVIDENCE AGAINST THE PRESENCE OF HORMONE-SENSITIVE LIPASE IN HUMAN MACROPHAGES

Cholesteryl ester-laden macrophages are the hallmark of the fatty stre aks that precede arteriosclerotic plaques in humans and experimental a nimals. This article studies several aspects of cytoplasmic cholestery l ester metabolism in cultured human monocyte-derived macrophages. Ade nosine 3',5'-cyclic monophosphate (cAMP) consistently inhibited choles teryl ester mobilization from cells that had been loaded with choleste ryl esters by preincubation with acetylated low-density lipoprotein. T his effect was observed in both the absence and presence of extracellu lar cholesterol accepters as well as with acyl coenzyme A:cholesterol acyltransferase inhibitors. In contrast, dibutyryl cAMP activated chol esteryl ester hydrolysis in J774 macrophages. Since hormone-sensitive lipase is thought to be responsible for the neutral cholesteryl ester hydrolytic activity in several cell types, we looked for the presence of its mRNA in our macrophages by means of reverse transcription coupl ed to the polymerase chain reaction technique. Hormone-sensitive lipas e mRNA was detected in J774 macrophages but not in human monocytes or in human monocyte-derived macrophages. These results demonstrated grea t differences in cholesteryl ester metabolism between macrophages of d ifferent origin. While hormone-sensitive lipase may be responsible for neutral cholesteryl ester hydrolytic activity in J774 macrophages, in human monocyte-derived macrophages it is not; thus, a different and a s yet unidentified enzyme must be present. (Arterioscler Thromb. 1994; 14:443-452.)