Inhibition of the acidification of endosomes and lysosomes by the antibiotic concanamycin B in macrophage J774

Abstract

The antibiotic concanamycin B was found to inhibit oxidized‐low‐density‐lipoprotein(LDL)‐induced accumulation of lipid droplets in the macrophage J774 at a concentration of 5–10 nM. Concanamycin B inhibited cholesteryl‐ester synthesis from [14C]oleate by 50% at 14 nM without affecting the synthesis of triacylglycerol and polar lipids. Degradation of internalized oxidized 125I‐LDL was inhibited by about 80% in cells treated with 25 nM concanamycin B, while cell‐surface binding of oxidized 125I‐LDL at 4°C, uptake of surface‐bound oxidized 125I‐LDL and microsomal acyl‐CoA: cholesterol acyltransferase activity were not significantly affected by the antibiotic at 25 nM. When J774 cells were treated with 25 nM concanamycin B at 37°C for 60 min, there was a reduction of about 50% in the activity of cell‐surface receptors. This reduction appeared to be due to partial trapping of the receptors within the cells. Concanamycin B significantly inhibited ATP‐dependent acidification of endosomes and lysosomes of the J774 cells at a concentration of 4 nM. Since acidic condition of these organelles is required for receptor recycling and hydrolysis of lipoproteins, the results demonstrate that concanamycin‐B inhibition of oxidized‐LDL‐induced accumulation of lipid droplets and cholesteryl esters in macrophages J774 is associated with reduced ATP‐dependent acidification of these organelles. Copyright © 1992, Wiley Blackwell. All rights reserved