Effect of cupric ion on cholesteryl ester hydrolysis in rat peritoneal macrophages

The inhibitory effects of Cu2+ on the hydrolysis of cholesteryl [4-14C]oleate droplets in rat peritoneal macrophages were studied. Macrophages rapidly incorporated cholesteryl [4-14C]oleate droplets and hydrolyzed at a linear rate over 9 h. When macrophages were preincubated in the medium containing Cu2+, the hydrolysis of cholesteryl oleate within macrophages was markedly inhibited by Cu2+ and eventually led to the accumulation of cholesteryl oleate in macrophages. The inhibitory effect on the hydrolysis of cholesteryl oleate was dependent on the concentration of Cu2+. Also, the activity of acid cholesteryl ester hydrolase (acid CEH) in lysosomal fractions isolated from rat peritoneal macrophages with Cu2+ showed a marked decrease. This decrease also occurred in a dose dependent manner. These results suggest that Cu2+ inhibits the hydrolysis of cholesteryl ester in macrophages, and that the accumulation of cholesteryl ester in macrophages of the early atheroscleotic lesion is responsible for the decrease of lysosomal acid CEH activity.