REDUCED EXPRESSION OF THE MACROPHAGE SCAVENGER RECEPTORS IN MACROPHAGE-LIKE CELL MUTANTS RESISTANT TO BREFELDIN-A

Brefeldin A (BFA)-resistant mutants, JB15, JB23 and JB33, were isolate d from mutagenized murine macrophage-like (J774) cells and their modif ied low density lipoprotein (LDL) metabolism was studied. When JB23 ce lls, the most resistant clone, were incubated with acetylated LDL, int racellular accumulation of cholesteryl esters (CE) was reduced by 31% as compared with J774 cells. The cell-association of I-125-acetyl-LDL with, and subsequent endocytic degradation by JB23 cells were reduced by 40-60% compared with J774 cells. Western and Northern blot analyses showed that the protein and mRNA levels of the macrophage scavenger r eceptors (MSR) were reduced by 68% and 55% respectively in JB23 cells as compared with those in J774 cells. These results indicate that a pu tative BFA-target molecule(s) might regulate MSR gene expression as we ll as macrophage-derived foam cell formation. (C) 1998 Academic Press.