Document Detail


Native low-density lipoprotein uptake by macrophage colony-stimulating factor-differentiated human macrophages is mediated by macropinocytosis and micropinocytosis.
MedLine Citation:
PMID:  20634472     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, N.I.H., Intramural     Date:  2010-07-15
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  30     ISSN:  1524-4636     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-16     Completed Date:  2010-10-12     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2022-31     Citation Subset:  IM    
Affiliation:
Section of Experimental Atherosclerosis, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md 20892-1422, USA.
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MeSH Terms
Descriptor/Qualifier:
Biological Transport, Active / 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:
0/Indoles; 0/Lipoproteins, LDL; 0/Macrolides; 0/SU 6656; 0/Sulfonamides; 81627-83-0/Macrophage Colony-Stimulating Factor; 88899-55-2/bafilomycin A1
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