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Reversible accumulation of cholesteryl esters in macrophages incubated with acetylated lipoproteins.
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MedLine Citation:
PMID:  229107     Owner:  NLM     Status:  MEDLINE    
Mouse peritoneal macrophages accumulate large amounts of cholesteryl ester when incubated with human low-density lipoprotein that has been modified by chemical acetylation (acetyl-LDL). This accumulation is related to a high-affinity cell surface binding site that mediates the uptake of acetyl-LDL by adsorptive endocytosis and its delivery to lysosomes. The current studies demonstrate that the cholesteryl ester accumulation can be considered in terms of a two-compartment model: (a) the incoming cholesteryl esters of acetyl-LDL are hydrolyzed in lysosomes, and (b) the resultant free cholesterol is re-esterified in the cytosol where the newly formed esters are stored as lipid droplets. The following biochemical and morphologic evidence supports the hydrolysis-re-esterification mechanism: (a) Incubation of macrophages with acetyl-LDL markedly increased the rate of cholesteryl ester synthesis from [14C]oleate, and this was accompanied by an increase in the acyl-CoA:cholesteryl acyltransferase activity of cell-free extracts. (b) When macrophages were incubated with reconstituted acetyl-LDL in which the endogenous cholesterol was replaced with [3H]-cholesteryl linoleate, the [3H]cholesteryl linoleate was hydrolyzed, and at least one-half of the resultant [3H]cholesterol was re-esterified to form [3H]cholesteryl oleate, which accumulated within the cell. The lysosomal enzyme inhibitor chloroquine inhibited the hydrolysis of the [3H]cholesteryl linoleate, thus preventing the formation of [3H]cholesteryl oleate and leading to the accumulation of unhydrolyzed [3H]cholesteryl linoleate within the cells. (c) In the electron microscope, macrophages incubated with acetyl-LDL had numerous cytoplasmic lipid droplets that were not surrounded by a limiting membrane. The time course of droplet accumulation was similar to the time course of cholesteryl ester accumulation as measured biochemically. (d) When acetyl-LDL was removed from the incubation medium, biochemical and morphological studies showed that cytoplasmic cholesteryl esters were rapidly hydrolyzed and that the resultant free cholesterol was excreted from the cell.
M S Brown; J L Goldstein; M Krieger; Y K Ho; R G Anderson
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of cell biology     Volume:  82     ISSN:  0021-9525     ISO Abbreviation:  J. Cell Biol.     Publication Date:  1979 Sep 
Date Detail:
Created Date:  1980-02-28     Completed Date:  1980-02-28     Revised Date:  2014-06-27    
Medline Journal Info:
Nlm Unique ID:  0375356     Medline TA:  J Cell Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  597-613     Citation Subset:  IM    
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MeSH Terms
Ascitic Fluid / cytology
Cholesterol Esters / metabolism*
Culture Techniques
Inclusion Bodies / ultrastructure
Lipoproteins, LDL / metabolism*
Lysosomes / metabolism
Macrophages / metabolism*,  ultrastructure
Grant Support
Reg. No./Substance:
0/Cholesterol Esters; 0/Lipids; 0/Lipoproteins, LDL

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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Journal Information
Journal ID (nlm-ta): J Cell Biol
ISSN: 0021-9525
ISSN: 1540-8140
Publisher: The Rockefeller University Press
Article Information
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Print publication date: Day: 1 Month: 9 Year: 1979
Volume: 82 Issue: 3
First Page: 597 Last Page: 613
ID: 2110476
Publisher Id: 80072214
PubMed Id: 229107

Reversible accumulation of cholesteryl esters in macrophages incubated with acetylated lipoproteins

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