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.
228
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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