Role of monocyte colony-stimulating factor in foam cell generation.
Recently, we reported that human monocyte colony-stimulating factor (M-CSF) stimulates the clearance of lipoproteins containing apoB100 via both low density lipoprotein receptor-dependent and -independent pathways in target cells of M-CSF, and reduces plasma cholesterol level (Journal of Biological Chemistry, 265:12869-12875, 1990). This suggests a linkage of cytokines to the metabolic regulation of plasma cholesterol. Furthermore, we found a significant role of M-CSF in cholesterol metabolism of human monocyte-derived macrophages. M-CSF enhanced not only the uptake of acetylated low density lipoprotein and oxidized low density lipoprotein in macrophages, but also the efflux of cholesterol from cholesterol-loaded macrophages. To elucidate in vivo effects of M-CSF on cholesterol efflux from tissues, we administered an intravenous injection of 3H-cholesterol (150 microCi) into WHHL rabbits 1 month before starting M-CSF treatment. We observed an increased cholesterol efflux from tissues to plasma high density lipoprotein after M-CSF treatment when cholesterol efflux was estimated as the change in specific radioactivity of plasma high density lipoprotein-cholesterol. This result suggests that M-CSF can enhance the excretion of cholesterol from target cells of M-CSF, such as cholesterol-loaded macrophages in the arterial wall, and reduce the rate of atherogenesis.
Yamada
N
N
Third Department of Internal Medicine, University of Tokyo, Japan.
Ishibashi
S
S
Shimano
H
H
Inaba
T
T
Gotoda
T
T
Harada
K
K
Shimada
M
M
Shiomi
M
M
Watanabe
Y
Y
Kawakami
M
M
D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology; D005487:Foam Cells / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000378:metabolism*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism*
D002788:Cholesterol Esters; D016207:Cytokines; D008077:Lipoproteins, LDL; D016173:Macrophage Colony-Stimulating Factor; D002784:Cholesterol