The scavenger receptor serves as a route for internalization of lysophosphatidylcholine in oxidized low density lipoprotein-induced macrophage proliferation

We have recently demonstrated that the growth of murine macrophages is induced by oxidized low density lipoprotein (OY-LDL) and that lysophosphatidylcholine (lyse-PC), a major phospholipid component of Ox-LDL, plays an essential role in its mitogenic effect, The present study was undertaken to further characterize the role of the macrophage scavenger receptor (MSR) in Ox-LDL-induced macrophage growth. The growth-stimulating effect of Ox-LDL on murine resident peritoneal macrophages was inhibited by maleylated bovine serum albumin (maleyl-BSA), a non-lipoprotein ligand for MSR but a poor carrier of lyse-PC, while maleyl-BSA itself failed to induce macrophage growth even in the presence of lyso-PC. Moreover, it competitively inhibited the endocytic uptake of I-125-Ox-LDL and the specific uptake of lyse-PC by MSR, whereas nonspecific lyse-PC transfer to cells was not affected. Furthermore, the Ox-LDL-induced cell growth of peritoneal macrophages obtained from MSR knockout mice was significantly weaker than that of macrophages obtained from their wild-type Littermates. Our results suggest that the MSR is an important and efficient internalization pathway for lyse-PC in Ox-LDL-induced macrophage growth.