| Native low-density lipoprotein uptake by macrophage colony-stimulating factor-differentiated human macrophages is mediated by macropinocytosis and micropinocytosis. | |
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MedLine Citation:
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PMID: 20634472 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: To examine the pinocytotic pathways mediating native low-density lipoprotein (LDL) uptake by human macrophage colony-stimulating factor-differentiated macrophages (the predominant macrophage phenotype in human atherosclerotic plaques). METHODS AND RESULTS: We identified the kinase inhibitor SU6656 and the Rho GTPase inhibitor toxin B as inhibitors of macrophage fluid-phase pinocytosis of LDL. Assessment of macropinocytosis by time-lapse microscopy revealed that both drugs almost completely inhibited macropinocytosis, although LDL uptake and cholesterol accumulation by macrophages were only partially inhibited (approximately 40%) by these agents. Therefore, we investigated the role of micropinocytosis in mediating LDL uptake in macrophages and identified bafilomycin A1 as an additional partial inhibitor (approximately 40%) of macrophage LDL uptake that targeted micropinocytosis. When macrophages were incubated with both bafilomycin A1 and SU6656, inhibition of LDL uptake was additive (reaching 80%), showing that these inhibitors target different pathways. Microscopic analysis of fluid-phase uptake pathways in these macrophages confirmed that LDL uptake occurs through both macropinocytosis and micropinocytosis. CONCLUSIONS: Our findings show that human macrophage colony-stimulating factor-differentiated macrophages take up native LDL by macropinocytosis and micropinocytosis, underscoring the importance of both pathways in mediating LDL uptake by these cells. |
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Authors:
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Joshua J Anzinger; Janet Chang; Qing Xu; Chiara Buono; Yifu Li; Francisco J Leyva; Bum-Chan Park; Lois E Greene; Howard S Kruth |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Intramural Date: 2010-07-15 |
Journal Detail:
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Title: Arteriosclerosis, thrombosis, and vascular biology Volume: 30 ISSN: 1524-4636 ISO Abbreviation: Arterioscler. Thromb. Vasc. Biol. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-09-16 Completed Date: 2010-10-12 Revised Date: 2012-05-07 |
Medline Journal Info:
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Nlm Unique ID: 9505803 Medline TA: Arterioscler Thromb Vasc Biol Country: United States |
Other Details:
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Languages: eng Pagination: 2022-31 Citation Subset: IM |
Affiliation:
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Section of Experimental Atherosclerosis, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md 20892-1422, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Biological Transport, Active
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drug effects Cell Differentiation / drug effects Cells, Cultured Humans Indoles / pharmacology Lipoproteins, LDL / metabolism* Macrolides / pharmacology Macrophage Colony-Stimulating Factor / pharmacology* Macrophages / cytology, drug effects*, metabolism* Microscopy, Immunoelectron Pinocytosis / drug effects, physiology* Sulfonamides / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Indoles; 0/Lipoproteins, LDL; 0/Macrolides; 0/SU 6656; 0/Sulfonamides; 81627-83-0/Macrophage Colony-Stimulating Factor; 88899-55-2/bafilomycin A1 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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