Macropinocytosis Is the Endocytic Pathway That Mediates Macrophage Foam Cell Formation with Native Low Density Lipoprotein

Previously, we reported that fluid-phase endocytosis of native LDL by PMA-activated human monocytederived macrophages converted these macrophages into cholesterol-enriched foam cells (Kruth, H. S., Huang, W., Ishii, I., and Zhang, W. Y. (2002) J. Biol. Chem. 277, 34573-34580). Uptake of fluid by cel...

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Bibliographic Details
Published in:The Journal of biological chemistry 2005-01, Vol.280 (3), p.2352-2360
Main Authors: Kruth, Howard S., Jones, Nancy L., Huang, Wei, Zhao, Bin, Ishii, Itsuko, Chang, Janet, Combs, Christian A., Malide, Daniela, Zhang, Wei-Yang
Format: Article
Language:English
Subjects:
Cells, Cultured
Chromones - pharmacology
Endocytosis
Enzyme Inhibitors - pharmacology
Foam Cells - drug effects
Foam Cells - metabolism
Foam Cells - ultrastructure
Humans
Immunohistochemistry
Lipoproteins, LDL - metabolism
Macrophage Activation - drug effects
Microscopy, Electron
Morpholines - pharmacology
Phosphoinositide-3 Kinase Inhibitors
Pinocytosis
Proton-Translocating ATPases - metabolism
Tetradecanoylphorbol Acetate - pharmacology
Vacuoles - enzymology
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Summary:Previously, we reported that fluid-phase endocytosis of native LDL by PMA-activated human monocytederived macrophages converted these macrophages into cholesterol-enriched foam cells (Kruth, H. S., Huang, W., Ishii, I., and Zhang, W. Y. (2002) J. Biol. Chem. 277, 34573-34580). Uptake of fluid by cells can occur either by micropinocytosis within vesicles (40-fold over its concentration in the culture medium consistent with macropinosome shrinkage by maturation into multivesicular body endosomes. Macropinocytosis of LDL taken up in the fluid phase without receptor-mediated binding of LDL is a novel endocytic pathway that generates macrophage foam cells. Macropinocytosis in macrophages and possibly other vascular cells is a new pathway to target for modulating foam cell formation in atherosclerosis.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M407167200