Document Detail


Helical apolipoproteins of high-density lipoprotein enhance phagocytosis by stabilizing ATP-binding cassette transporter A7.
MedLine Citation:
PMID:  20495215     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We previously reported that the endogenous ATP-binding cassette transporter (ABC)A7 strongly associates with phagocytic function rather than biogenesis of high-density lipoprotein (HDL), being regulated by sterol-regulatory element binding protein (SREBP)2. Phagocytic activity was found enhanced by apolipoprotein (apo)A-I and apoA-II more than twice the maximum in J774 and mouse peritoneal macrophages. Therefore we investigated the molecular basis of this reaction in association with the function of ABCA7. Similar to ABCA1, ABCA7 was degraded, likely by calpain, and apoA-I and apoA-II stabilize ABCA7 against degradation. Cell surface biotinylation experiments demonstrated that endogenous ABCA7 predominantly resides on the cell surface and that the apolipoproteins increase the surface ABCA7. The increase of phagocytosis by apolipoproteins was retained in the J774 cells treated with ABCA1 siRNA and in the peritoneal macrophages from ABCA1-knockout mice, but it was abolished in the J774 cells treated with ABCA7 siRNA and in the peritoneal macrophages from ABCA7-knockout mice. Phagocytosis was decreased in the cells in the peritoneal cavity of the ABCA7-knockout mouse compared with the wild-type control. We thus concluded that extracellular helical apolipoproteins augment ABCA7-associated phagocytosis by stabilizing ABCA7. The results demonstrated direct enhancement of the host defense system by HDL components.
Authors:
Nobukiyo Tanaka; Sumiko Abe-Dohmae; Noriyuki Iwamoto; Michael L Fitzgerald; Shinji Yokoyama
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-05-22
Journal Detail:
Title:  Journal of lipid research     Volume:  51     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-12     Completed Date:  2011-02-14     Revised Date:  2011-09-13    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2591-9     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
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MeSH Terms
Descriptor/Qualifier:
ATP-Binding Cassette Transporters / genetics,  metabolism*
Animals
Apolipoprotein A-I / pharmacology
Apolipoprotein A-II / pharmacology
Apolipoproteins* / chemistry,  metabolism
Cell Line
Fibroblasts / cytology,  drug effects,  metabolism
Humans
Lipoproteins, HDL* / chemistry,  metabolism
Macrophages, Peritoneal / cytology,  drug effects,  metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Phagocytosis / physiology*
RNA, Small Interfering / genetics,  metabolism
Staphylococcus aureus / metabolism
Grant Support
ID/Acronym/Agency:
HL-074136/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/ATP binding cassette transporter 1; 0/ATP-Binding Cassette Transporters; 0/Abca7 protein, mouse; 0/Apolipoprotein A-I; 0/Apolipoprotein A-II; 0/Apolipoproteins; 0/Lipoproteins, HDL; 0/RNA, Small Interfering
Comments/Corrections

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