RRC ID |
38199
|
著者 |
Tanaka N, Abe-Dohmae S, Iwamoto N, Fitzgerald ML, Yokoyama S.
|
タイトル |
Helical apolipoproteins of high-density lipoprotein enhance phagocytosis by stabilizing ATP-binding cassette transporter A7.
|
ジャーナル |
J Lipid Res
|
Abstract |
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.
|
巻・号 |
51(9)
|
ページ |
2591-9
|
公開日 |
2010-9-1
|
DOI |
10.1194/jlr.M006049
|
PII |
S0022-2275(20)42289-8
|
PMID |
20495215
|
PMC |
PMC2918442
|
MeSH |
ATP Binding Cassette Transporter 1
ATP-Binding Cassette Transporters / genetics
ATP-Binding Cassette Transporters / metabolism*
Animals
Apolipoprotein A-I / pharmacology
Apolipoprotein A-II / pharmacology
Apolipoproteins* / chemistry
Apolipoproteins* / metabolism
Cell Line
Fibroblasts / cytology
Fibroblasts / drug effects
Fibroblasts / metabolism
Humans
Lipoproteins, HDL* / chemistry
Lipoproteins, HDL* / metabolism
Macrophages, Peritoneal / cytology
Macrophages, Peritoneal / drug effects
Macrophages, Peritoneal / metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Phagocytosis / physiology*
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
Staphylococcus aureus / metabolism
|
IF |
4.483
|
引用数 |
29
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
リソース情報 |
ヒト・動物細胞 |
BALB/3T3 |