Decrease in Scavenger Receptor Expression in Human Monocyte–Derived Macrophages Treated With Granulocyte Macrophage Colony-Stimulating Factor
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TL;DR: Results indicate that GM-CSF can downregulate both types I and II scavenger receptor in human monocyte-derived macrophages, which might have implications for foam cell formation.
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Abstract: To determine whether scavenger receptors are susceptible to regulation by granulocyte macrophage colony-stimulating factor (GM-CSF), a macrophage-specific cytokine, human monocytes were differentiated into macrophages in the absence or presence of 20 U/mL GM-CSF. Binding, uptake, and degradation of acetylated LDL (Ac-LDL) and oxidized LDL (Ox-LDL) were measured. Treatment with GM-CSF resulted in a significant twofold to threefold decrease in the number of binding sites for Ac-LDL and Ox-LDL on the surface of macrophages without affecting the affinity of the receptor for these ligands. Competition experiments revealed that two binding sites were responsible for the recognition and uptake of Ac-LDL: one specific for Ac-LDL and one that recognized both Ac-LDL and Ox-LDL. No binding site specific for Ox-LDL could be detected in either control or GM-CSF–treated macrophages. Treatment of human monocyte–derived macrophages with GM-CSF resulted in a decrease of the Ac-LDL/Ox-LDL receptor but did not affect the binding site specific for Ac-LDL. Northern blot analysis showed that mRNA levels of both types I and II scavenger receptor were reduced in macrophages differentiated in the presence of GM-CSF. Human macrophages that were differentiated in the presence of GM-CSF accumulated ≈50% fewer cholesteryl esters. Taken together, these results indicate that GM-CSF can downregulate both types I and II scavenger receptor in human monocyte–derived macrophages, which might have implications for foam cell formation.
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Citations
Macrophage scavenger receptor class A: A multifunctional receptor in atherosclerosis.
TL;DR: Macrophage scavenger receptor class A is thought to be one of the main receptors involved in foam cell formation, mediating the influx of lipids into the macrophages, and has been shown to be important in the inflammatory response in host defense, cellular activation, adhesion, and cell-cell interaction.
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Receptors for oxidized low density lipoprotein
TL;DR: The objective of this article is to review the most important publications dealing with structure, ligand specificity, regulation, and function of scavenger receptors.
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Hepatic and extrahepatic scavenger receptors: function in relation to disease
TL;DR: Scavenger receptors (SRs) have been of major interest in the study of atherogenesis over the past decade as discussed by the authors, and several new members of the SR family have been cloned on the basis of their ability to recognize modified lipoproteins.
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GM-CSF Deficiency Reduces Macrophage PPAR-γ Expression and Aggravates Atherosclerosis in ApoE-Deficient Mice
TL;DR: GM-CSF deficiency increases atherosclerosis under hypercholesterolemic conditions, indicating antiatherogenic role for GM- CSF, and it is suggested this protective role is mediated by PPAR-&ggr; and ABCA1, molecules that affect cholesterol homeostasis and inflammation.
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Expression of lipoprotein receptors in atherosclerotic lesions
TL;DR: It is evident that no single receptor pathway is solely responsible for the increased lipid uptake in lesion cells but several redundant mechanisms may contribute to the uptake and degradation of lipoproteins in atherosclerotic lesions.
64
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Platelet secretory products inhibit lipoprotein metabolism in macrophages.
TL;DR: This study demonstrates that human blood platelets secrete a product that inhibits the binding and uptake of AcAc LDL by mouse peritoneal macrophage and the subsequent accumulation of cholesteryl esters, the first indication that an endogenous macromolecule interacts with Ac LDL receptor on macrophages.
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Macrophage colony-stimulating factor regulates both activities of neutral and acidic cholesteryl ester hydrolases in human monocyte-derived macrophages.
Toshimori Inaba,Hitoshi Shimano,Takanari Gotoda,Kenji Harada,Masako Shimada,Masako Kawamura,Yoshio Yazaki,N. Yamada +7 more
TL;DR: The results suggest that M- CSF enhances net hydrolysis of CE by stimulating the two CE hydrolases to a greater extent than ACAT, and M-CSF may reduce the rate of atherogenesis.
Characterization of the interaction of acetylated LDL and oxidatively modified LDL with human liver parenchymal and Kupffer cells in culture.
TL;DR: It is concluded that human liver parenchymal cells contain a scavenger receptor that interacts with Ac-LDL and Ox- LDL and an additional recognition site that recognizes Ox-LD lysosomes specifically.
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Effects of human recombinant macrophage colony-stimulating factor on the secretion of lipoprotein lipase from macrophages.
Natsuko Mori,Takanari Gotoda,Shun Ishibashi,Hitoshi Shimano,Kenji Harada,Toshimori Inaba,Fumimaro Takaku,Yoshio Yazaki,Nobuhiro Yamada +8 more
TL;DR: The results indicate that the stimulation of lipoprotein lipase secretion after M-CSF treatment was evident in rat alveolar macrophages and human monocyte-derived macrophage on the basis of both enzyme activity and mRNA level; therefore, M- CSF may be involved in lipop protein metabolism of macrophaging through modulation of the secretion of lipo-lipase.
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Involvement of the macrophage low density lipoprotein receptor-binding domains in the uptake of oxidized low density lipoprotein.
TL;DR: The ac-LDL and LDL receptor-binding domains as well as a unique epitope on the amino terminus of apo B-100 may be involved in macrophage binding of ox- LDL.
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