RRC ID 38199
Author Tanaka N, Abe-Dohmae S, Iwamoto N, Fitzgerald ML, Yokoyama S.
Title Helical apolipoproteins of high-density lipoprotein enhance phagocytosis by stabilizing ATP-binding cassette transporter A7.
Journal 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.
Volume 51(9)
Pages 2591-9
Published 2010-9
DOI 10.1194/jlr.M006049
PII jlr.M006049
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 4.743
Times Cited 29
Human and Animal Cells