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J. Biol. Chem., Vol. 265, Issue 24, 14109-14117, Aug, 1990
S Ishibashi, T Inaba, H Shimano, K Harada, I Inoue, H Mokuno, N Mori, T Gotoda, F Takaku and N Yamada
We have investigated effects of monocyte colony-stimulating factor (M- CSF)
on the uptake of acetylated low density lipoproteins (acetyl-LDL) and the
activity of cholesterol esterification in human monocyte- derived
macrophage. The cells were cultured with M-CSF for 10 days and then
incubated with acetyl-LDL for 24 h. M-CSF (128 ng/ml) enhanced the uptake
and degradation of 10 micrograms/ml of 125I-acetyl LDL 7.5-fold (n = 6) and
the effect of M-CSF was dose-dependent at the concentrations of 0.5-32
ng/ml. The binding experiments at 4 degrees C demonstrated that the number
of acetyl-LDL receptor was increased by the addition of M-CSF. Supporting
this, ligand blotting analysis revealed a significant increase in a
receptor protein for acetyl-LDL (240 kDa). Binding of LDL was also enhanced
by M-CSF but less significantly than that of acetyl-LDL. Cellular
cholesterol esterification in the presence of 10 micrograms/ml acetyl-LDL
was enhanced 24.1-fold (n = 13) by 128 ng/ml M-CSF. It was evident that M-
CSF enhanced cholesterol esterification to a greater extent than the
cellular uptake of acetyl-LDL (24.1- versus 7.5-fold). Cholesterol
esterification was also enhanced by the addition of granulocyte- macrophage
colony-stimulating factor and interleukin 1. We conclude that M-CSF
enhances the uptake of both acetyl-LDL and LDL by increasing their receptor
number, and further enhances the process of cholesterol esterification,
resulting in a remarkable increase in cholesterol esterification in
macrophages. These findings strongly suggest the significant involvement of
cytokines such as M-CSF in cholesterol metabolism of macrophages.
Monocyte colony-stimulating factor enhances uptake and degradation of acetylated low density lipoproteins and cholesterol esterification in human monocyte-derived macrophages
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
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