INDUCTION OF MURINE MACROPHAGE GROWTH BY MODIFIED LDLS

We previously reported that cell membrane components and lipoproteins were able to induce the growth of murine peritoneal macrophages. The aim of the present study was to examine whether macrophage growth could also be induced by chemically modified lipoproteins, such as acetylated low density lipoprotein (acetyl-LDL) or oxidized LDL, ligands known to be endocytosed by the macrophage scavenger receptors. When murine peritoneal exudate macrophages were cultured in vitro with 25-100 mug/mL acetyl-LDL or oxidized LDL, significant growth was induced. On comparing the dose-response curves of these LDLs, a more potent effect was seen with oxidized LDL than acetyl-LDL, especially on resident macrophages. On the other hand, growth of these cells was not stimulated by native (unmodified) LDL or high density lipoprotein. These in vitro data revealed a new function of chemically modified LDLs as effective inducers of macrophage cell growth. This aspect may be physiologically relevant to the growth of macrophage foam cells in situ in the development of atherosclerosis.