title: Differential regulation of macropinocytosis in macrophages by cytokines: implications for foam cell formation and atherosclerosis.
abstract: A key event during the formation of lipid-rich foam cells during the progression of atherosclerosis is the uptake of modified low-density lipoproteins (LDL) by macrophages in response to atherogenic mediators in the arterial intima. In addition to scavenger receptor-dependent uptake of LDL, macropinocytosis is known to facilitate the uptake of LDL through the constitutive and passive internalization of large quantities of extracellular solute. In this study we confirm the ability of macropinocytosis to facilitate the uptake of modified LDL by human macrophages and show its modulation by TGF-β, IFN-γ, IL-17A and IL-33. Furthermore we show that the TGF-β-mediated inhibition of macropinocytosis is a Smad-2/-3-independent process.
authors.affiliation: Cardiff School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3AX, United Kingdom. Electronic address: darynmichael@hotmail.com.
authors.forename: Daryn R
authors.initials: DR
authors.lastname: Michael
authors.forename: Tim G
authors.initials: TG
authors.lastname: Ashlin
authors.forename: Charlotte S
authors.initials: CS
authors.lastname: Davies
authors.forename: Hayley
authors.initials: H
authors.lastname: Gallagher
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Stoneman
authors.forename: Melanie L
authors.initials: ML
authors.lastname: Buckley
authors.forename: Dipak P
authors.initials: DP
authors.lastname: Ramji
mesh_terms: D050197:Atherosclerosis / Q000276:immunology / Q000473:pathology*; D001692:Biological Transport / Q000187:drug effects; D002454:Cell Differentiation; D002478:Cells, Cultured; D015638:Cytochalasin D / Q000494:pharmacology; D005487:Foam Cells / Q000276:immunology / Q000473:pathology*; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism*; D000067596:Interleukin-33; D007378:Interleukins / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010873:Pinocytosis / Q000187:drug effects*; D034622:RNA Interference; D034741:RNA, Small Interfering; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: C508717:IL17A protein, human; C506536:IL33 protein, human; D020381:Interleukin-17; D000067596:Interleukin-33; D007378:Interleukins; D008077:Lipoproteins, LDL; D019384:Nucleic Acid Synthesis Inhibitors; D034741:RNA, Small Interfering; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; D015638:Cytochalasin D; D007371:Interferon-gamma; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)
keywords: 1,1-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyane perchlorate; AcLDL; Apo; Atherosclerosis; BMDM; CD-36; Cytokine; DiI; Foam cell; GAPDH; HMDM; IFN-γ; IL; LDL; LY; Low density lipoprotein; Macropinocytosis; OxLDL; SR-A; TGF-β; THP-1; acetylated LDL; apolipoprotein; bone marrow-derived macrophage; cluster of differentiation 36; glyceraldehyde 3-phosphate dehydrogenase; human acute monocytic leukemia cells; human monocyte-derived macrophages; interferon-γ; interleukin; low-density lipoproteins; lucifer yellow; oxidized LDL; scavenger receptor A; shRNA; short hairpin RNA; transforming growth factor-β