Neutral lipid accumulation in macrophages during lipid-induced macrophage growth

We previously reported that lipids such as cholesterol esters, triglycerides, and some phospholipids that are components of cell membranes or serum lipoproteins induced the growth of mouse peritoneal macrophages in vitro. Here, we report that macrophage growth was directly induced by lipids without any soluble factors and that the continuous presence of lipids was required for their growth during culture. When macrophages were cultured with several phospholipids that stimulated macrophage growth, their triglyceride content was dramatically increased during culture, whereas their contents of phospholipids, cholesterol, and esterified cholesterols were scarcely changed. On the other hand, phosphatidylcholine and sphingomyelin, which did not stimulate macrophage growth, caused less accumulation of triglycerides in the cells. Macrophages in which triglycerides accumulated resembled foam cells, since they contained many particles that stained with oil red O. Macrophages that cultured with cholesteryl linoleate also contained many oil red O-stainable particles. These data suggest that accumulation of lipid droplets is correlated with macrophage growth induced by lipids and that foam cells in pathological states such as those in atherosclerotic or xanthoma lesions might proliferate in situ.