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Macrophage ABCA1 reduces MyD88-dependent Toll-like receptor trafficking to lipid rafts by reduction of lipid raft cholesterol


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dc.contributorElizabeth Schwartz, ehs0009@auburn.eduen_US
dc.creatorZhu, Xuewei
dc.creatorOwen, John S.
dc.creatorWilson, Martha D.
dc.creatorLi, Haitao
dc.creatorGriffiths, Gary L.
dc.creatorThomas, Michael J.
dc.creatorHiltbold, Elizabeth M.
dc.creatorFessler, Michael B.
dc.creatorParks, John S.
dc.date.accessioned2022-03-11T05:49:21Z
dc.date.available2022-03-11T05:49:21Z
dc.date.created2010-11
dc.identifier10.1194/jlr.M006486en_US
dc.identifier.urihttp://www.jlr.org/content/51/11/3196.abstracten_US
dc.identifier.urihttps://aurora.auburn.edu/handle/11200/50041
dc.identifier.urihttp://dx.doi.org/10.35099/aurora-110
dc.description.abstractWe previously showed that macrophages from macrophage-specifi c ATP-binding cassette transporter A1 (ABCA1) knockout (Abca1(-M/-M)) mice had an enhanced proinflammatory response to the Toll-like receptor (TLR) 4 agonist, lipopolysaccharide (LPS), compared with wild-type (WT) mice. In the present study, we demonstrate a direct association between free cholesterol (FC), lipid raft content, and hyper-responsiveness of macrophages to LPS in WT mice. Abca1(-M/-M) macrophages were also hyper-responsive to specific agonists to TLR2, TLR7, and TLR9, but not TLR3, compared with WT macrophages. We hypothesized that ABCA1 regulates macrophage responsiveness to TLR agonists by modulation of lipid raft cholesterol and TLR mobilization to lipid rafts. We demonstrated that Abca1(-M/-M) vs. WT macrophages contained 23% more FC in isolated lipid rafts. Further, mass spectrometric analysis suggested raft phospholipid composition was unchanged. Although cell surface expression of TLR4 was similar between Abca1(-M/-M) and WT macrophages, significantly more TLR4 was distributed in membrane lipid rafts in Abca1(-M/-M) macrophages. Abca1(-M/-M) macrophages also exhibited increased trafficking of the predominantly intracellular TLR9 into lipid rafts in response to TLR9-specifi c agonist (CpG). Collectively, our data suggest that macrophage ABCA1 dampens inflammation by reducing MyD88-dependent TLRs trafficking to lipid rafts by selective reduction of FC content in lipid rafts.en_US
dc.formatPDFen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biologyen_US
dc.relation.ispartofJournal of Lipid Researchen_US
dc.relation.ispartofseries0022-2275en_US
dc.rightsThis is the version of record published by PUBLISHER and is made available under the CC-BY 4.0 license. Item should be cited as: Zhu, X., Owen, J. S., Wilson, M. D., Li, H., Griffiths, G. L., Thomas, M. J., ... & Parks, J. S. (2010). Macrophage ABCA1 reduces MyD88-dependent Toll-like receptor trafficking to lipid rafts by reduction of lipid raft cholesterol [S]. Journal of lipid research, 51(11), 3196-3206.en_US
dc.subjectfree cholesterolen_US
dc.subjectcytokinesen_US
dc.subjectimmunologyen_US
dc.subjectlipid dropletsen_US
dc.subjectlymphocytesen_US
dc.subjectretinoidsen_US
dc.subjectINNATE IMMUNE RECOGNITIONen_US
dc.subjectCASSETTE TRANSPORTER A1en_US
dc.subjectTANGIER-DISEASEen_US
dc.subjectABCA1-DEFICIENT MACROPHAGESen_US
dc.subjectPLASMA-MEMBRANEen_US
dc.subjectAPOA-Ien_US
dc.subjectATHEROSCLEROSISen_US
dc.subjectActivationen_US
dc.subjectExpressionen_US
dc.subjectAccumulationen_US
dc.titleMacrophage ABCA1 reduces MyD88-dependent Toll-like receptor trafficking to lipid rafts by reduction of lipid raft cholesterolen_US
dc.typeTexten_US
dc.type.genreJournal Article, Academic Journalen_US
dc.citation.volume51en_US
dc.citation.issue11en_US
dc.citation.spage3196en_US
dc.citation.epage3206en_US
dc.description.statusPublisheden_US
dc.description.peerreviewYesen_US

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