Role of macrophage colony-stimulating factor in the initial process of atherosclerosis.

The early atherosclerotic lesion is characterized by the presence of macrophage-derived foam cells. Macrophage colony-stimulating factor (M-CSF) specifically stimulates the functions of the monocyte-macrophages. To elucidate the role of M-CSF in the atherogenic process in vitro and in vivo, we studied the effects of M-CSF on enzyme activities of acidic cholesteryl ester (CE) hydrolase, neutral CE hydrolase, and acyl-coenzyme A:cholesterol acyltransferase (ACAT), and 300 micrograms of M-CSF was intravenously injected into WHHL rabbits aged 2.5 months for 8.5 months. M-CSF (100 ng/ml) enhanced acidic and neutral CE hydrolase, and ACAT activities by 3.2-fold, 4-fold, and 2.3-fold, respectively, in the presence of acetyl LDL, and M-CSF increased ratios of both acidic and neutral CE hydrolase activities to ACAT activity. After M-CSF injection into WHHL rabbits, we found very retarded progression of atherosclerosis. The accumulation of cholesterol ester was remarkably decreased in the aortae of M-CSF-treated animals (0.60 +/- 0.32 mg/g tissue), as compared to those of controls (4.21 +/- 0.65 mg/g tissue). The results suggest that M-CSF prevents the progression of atherosclerosis in WHHL rabbits by increasing net hydrolysis of cholesteryl ester in macrophages.