Constitutive Receptor-independent Low Density Lipoprotein Uptake and Cholesterol Accumulation by Macrophages Differentiated from Human Monocytes with Macrophage-Colony-stimulating Factor (M-CSF)
| Autor: | Masahiro Mori, Howard S. Kruth, Bin Zhao, Yifu Li, Stephen W. Waldo, Chiara Buono, Nancy L. Jones |
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| Rok vydání: | 2006 |
| Předmět: |
Macrophage colony-stimulating factor
medicine.medical_specialty medicine.medical_treatment Receptors Cytoplasmic and Nuclear Biology Endocytosis Biochemistry Monocytes chemistry.chemical_compound Internal medicine medicine Humans Macrophage Molecular Biology Constitutive Androstane Receptor Foam cell Cholesterol Macrophage Colony-Stimulating Factor Macrophages Cell Differentiation Cell Biology Molecular biology Interleukin-10 Lipoproteins LDL Cytokine Endocrinology chemistry Low-density lipoprotein lipids (amino acids peptides and proteins) Fetal bovine serum Transcription Factors |
| Zdroj: | Journal of Biological Chemistry. 281:15757-15762 |
| ISSN: | 0021-9258 |
| Popis: | Recently, we have shown that macrophage uptake of low density lipoprotein (LDL) and cholesterol accumulation can occur by nonreceptor mediated fluid-phase macropinocytosis when macrophages are differentiated from human monocytes in human serum and the macrophages are activated by stimulation of protein kinase C (Kruth, H. S., Jones, N. L., Huang, W., Zhao, B., Ishii, I., Chang, J., Combs, C. A., Malide, D., and Zhang, W. Y. (2005) J. Biol. Chem. 280, 2352-2360). Differentiation of human monocytes in human serum produces a distinct macrophage phenotype. In this study, we examined the effect on LDL uptake of an alternative macrophage differentiation phenotype. Differentiation of macrophages from human monocytes in fetal bovine serum with macrophage-colony-stimulating factor (M-CSF) produced a macrophage phenotype demonstrating constitutive fluid-phase uptake of native LDL leading to macrophage cholesterol accumulation. Fluid-phase endocytosis of LDL by M-CSF human macrophages showed non-saturable uptake of LDL that did not down-regulate over 48 h. LDL uptake was mediated by continuous actin-dependent macropinocytosis of LDL by these M-CSF-differentiated macrophages. M-CSF is a cytokine present within atherosclerotic lesions. Thus, macropinocytosis of LDL by macrophages differentiated from monocytes under the influence of M-CSF is a plausible mechanism to account for macrophage foam cell formation in atherosclerotic lesions. This mechanism of macrophage foam cell formation does not depend on LDL modification or macrophage receptors. |
| Databáze: | OpenAIRE |
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