Exposure of macrophages to PLA2-modified lipoproteins leads to cellular lipid accumulations.

After a 24-h exposure of mouse peritoneal macrophages to LDL, of which the phospholipids were reduced to 30% by phospholipase A2 (PLA2)-treatment, the cellular level of free and esterified cholesterol was elevated 1.9- and 5.0-fold, respectively. Furthermore, the activity of the cytosolic acyl-CoA cholesterol acyl-transferase (ACAT), which was calculated from the rate of 14C-oleate incorporation into the cellular cholesteryl esters, increased with the degree of LDL hydrolysis. The incubation of macrophages with native HDL led to decreased labeling of cellular cholesteryl esters. However, after PLA2-treatment of HDL the esterification rate increased with the degree of hydrolysis analogous to PLA2-modified LDL. The formation of numerous intracellular lipid droplets was observed by light microscopy after staining with Sudan-III. These data suggest that phospholipases A2 may play a role in the transformation of macrophages into foam-cells, a hallmark of early atherosclerotic lesions.