MACROPHAGE-COLONY-STIMULATING FACTOR REGULATES BOTH ACTIVITIES OF NEUTRAL AND ACIDIC CHOLESTERYL ESTER HYDROLASES IN HUMAN MONOCYTE-DERIVEDMACROPHAGES

Macrophage colony-stimulating factor (M-CSF) regulates cholesterol met abolism in vivo and in vitro. We studied the effects of M-CSF on enzym e activities of acidic cholesteryl ester (CE) hydrolase, neutral CE hy drolase, and acyl-coenzyme A:cholesterol acyltransferase (ACAT), all o f which are involved in cellular cholesterol metabolism in macrophages . During the differentiation of monocytes to macrophages, these enzyme activities were induced and further enhanced in response to M-CSF. M- CSF (100 ng/ml) enhanced acidic and neutral CE hydrolase and ACAT acti vities by 3.2-, 4-, and 2.3-fold, respectively, in the presence of ace tyl LDL. The presence of acetyl LDL influenced these enzyme activities . ACAT and acidic CE hydrolase activities were increased and neutral C E hydrolase activity was decreased, indicating that these enzymes are regulated by intracellular cholesterol enrichment. M-CSF increased the ratios of acidic CE hydrolase to ACAT activity and of neutral CE hydr olase to ACAT activity. The results suggest that M-CSF enhances net hy drolysis of CE by stimulating the two CE hydrolases to a greater exten t than ACAT, and M-CSF may reduce the rate of atherogenesis.