Induction of LDL receptor-related protein during the differentiation of monocyte-macrophages. Possible involvement in the atherosclerotic process.

Abstract

The low-density lipoprotein receptor-related protein (LRP) is a multifunctional receptor that binds to apolipoprotein E-rich lipoproteins, lipoprotein lipase, alpha 2-macroglobulin, lactoferrin, and tissue plasminogen activator. We studied the mRNA expression of LRP in human monocyte-derived macrophages and THP-1 cells. mRNA expression of LRP was induced during cell differentiation from human monocytes to macrophages or after incubation with phorbol ester (tetradecanoylphorbol acetate 100 ng/mL) in THP-1 cells, and the addition of 30 ng/mL macrophage colony-stimulating factor further enhanced LRP expression. These results indicated that the expression of LRP depended on the stage of differentiation and maturation of monocytic cells. mRNA expression of LRP was also enhanced in human monocyte-derived macrophages in the presence of acetylated low-density lipoprotein and in aorta of rabbits fed a high-cholesterol diet. We hypothesize that the LRP induced in monocyte-derived macrophages is involved in the initial process of atherosclerosis by interacting with its multiple ligands.