Stimulation of a neutral cholesteryl ester hydrolase by cAMP system in P388D 1 macrophages

Abstract

Cholesteryl ester laden foam cells in atherosclerotic lesions derive, in part, from macrophages. Mobilization of stored cholesteryl esters involves hydrolysis by a neutral cholesteryl ester hydrolase. Incubation of intact P388D 1 macrophages with dibutyryl cAMP in the presence of 1-methyl-3-isobutylxanthine resulted in a dose-dependent increase in neutral cholesteryl ester hydrolase activity of up to 50% (ED 50 = 0.1 mM). Incubation with prostaglandin E 1 in the presence of 1-methyl-3-isobutylxanthine also increased neutral cholesterol ester hydrolase activity by about 50%. In cell-free preparation, cAMP-dependent protein kinase caused about a 2-fold activation of the neutral cholesteryl ester hydrolase. Activation was blocked by protein kinase inhibitor. These data suggest that the P388D 1 macrophage may be a useful model for studying the hormonal regulation of cholesteryl ester mobilization in macrophage-derived foam cells.