INHIBITION OF THE UPTAKE OF OXIDIZED LOW-DENSITY-LIPOPROTEIN IN MACROPHAGE-J774 BY THE ANTIBIOTIC IKARUGAMYCIN

The antiprotozoal antibiotic ikarugamycin was found to significantly inhibit oxidized low-density lipoprotein(LDL)-induced accumulation of cholesteryl ester in macrophage J774 at a concentration over 1-4-mu-M. Cholesteryl ester synthesis from [C-14]oleate in the macrophages was similarly inhibited by the antibiotic, while the synthesis of triacylglycerol and polar lipids was not affected. The internalization of oxidized [I-125]LDL in macrophages was reduced to 50% by 2-mu-M ikarugamycin, while cell-surface binding of oxidized [I-125]LDL, lysosomal hydrolysis of the internalized oxidized [I-125]LDL and microsomal acyl-coenzyme A: cholesterol acyltransferase was not detectably inhibited by 5-mu-M ikarugamycin. The results demonstrated that ikarugamycin inhibited cholesteryl ester accumulation in macrophage J774 by specifically inhibiting the uptake of oxidized LDL.