Abstract
To identify the HDL3-binding proteins on human macrophages, we examined the involvement of GPI-anchored protein in the binding of HDL3, and tried to purify HDL3-binding protein. From membrane fractions of macrophages, we obtained 80- and 130-kDa HDL3-binding proteins by ligand blotting. Treatment of macrophages with phosphatidylinositol-specific phospholipase C (PI-PLC) significantly decreased the specific HDL3-binding in a dose-dependent manner. Furthermore, treatment with mannosamine, which blocks GPI-anchor formation, decreased specific HDL3-binding in a dose-dependent manner. PI-PLC treatment released from the cells the proteins with an M(r) of 80 kDa, which could also bind HDL3. PI-PLC as well as mannosamine treatment markedly reduced cholesterol efflux from macrophages in association with the decreased HDL-binding. Using HDL3-affinity chromatography, we purified 80-kDa GPI-anchored type HDL3-binding protein. In summary, we demonstrate the implication of 80-kDa GPI-anchored protein in the binding of HDL3 to human macrophages, which might have some role in reverse cholesterol transport.
Copyright 2000 Academic Press.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Binding Sites / drug effects
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Biological Transport / drug effects
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Carrier Proteins / antagonists & inhibitors
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Carrier Proteins / chemistry
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Carrier Proteins / isolation & purification*
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Carrier Proteins / metabolism*
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Cell Membrane / drug effects
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Cell Membrane / metabolism
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Cells, Cultured
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Cholesterol / metabolism
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Chromatography, Affinity
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Dose-Response Relationship, Drug
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Glycosylphosphatidylinositols / antagonists & inhibitors
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Glycosylphosphatidylinositols / metabolism*
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Hexosamines / pharmacology
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Humans
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Ligands
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Lipoproteins, HDL / antagonists & inhibitors
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Lipoproteins, HDL / metabolism*
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Lipoproteins, LDL / pharmacology
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Macrophages / chemistry*
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Macrophages / cytology
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Macrophages / drug effects
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Macrophages / metabolism
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Membrane Proteins / antagonists & inhibitors
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Membrane Proteins / chemistry
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Membrane Proteins / isolation & purification*
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Membrane Proteins / metabolism
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Molecular Probe Techniques
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Molecular Weight
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Phosphatidylinositol Diacylglycerol-Lyase
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Phosphoinositide Phospholipase C
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Protein Binding / drug effects
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Substrate Specificity
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Type C Phospholipases / metabolism
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Type C Phospholipases / pharmacology
Substances
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Carrier Proteins
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Glycosylphosphatidylinositols
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Hexosamines
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Ligands
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Lipoproteins, HDL
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Lipoproteins, LDL
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Membrane Proteins
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acetyl-LDL
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mannosamine
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Cholesterol
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Type C Phospholipases
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Phosphoinositide Phospholipase C
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Phosphatidylinositol Diacylglycerol-Lyase