Mechanisms for Macropahge Growth Induced by Oxidized Low Density Lipoprotein: the Role of Lysophosphatidylcholine

We recently demonstrated that murine macrophage growth is induced by oxidized low density lipoprotein (Ox-LDL). The present study was undertaken to elucidate the mechanisms for Ox-LDL-induced macrophage growth. Whereas the mitogenic activity of acetylated LDL (acetyl-LDL) for murine resident peritoneal macrophages was negligible, treatment of acetyl-LDL with phospholipase A2 led to an increase in lysophosphatidyl-choline (Lyso-PC), and a concomitant increase in its mitogenic effect, indicating an essential role of Lyso-PC in macrophage growth. The role of the scavenger receptor was also examined. Maleylated bovine serum albumin (M-BSA), an effective ligand for the scavenger receptor but a poor carrier of Lyso-PC, did not induce macrophage growth even in the presence of Lyso-PC whereas acetyl-LDL induced cell growth in the presence of Lyso-PC. Moreover, Ox-LDL induced macrophage growth was inhibited by 70% by the presence of M-BSA. M-BSA competitively inhibited the scavenger receptor-mediated endocytic uptake of Ox-LDL, thus reducing concomitant up-take of Lyso-PC, whereas non-specific direct transfer of Lyso-PC from Ox-LDL to cell surface was not affected. These results suggest that internalization of Lyso-PC through the scavenger receptor is a keystep to generate an intracellular signal for macrophage growth.