Human scavenger protein AIM increases foam cell formation and CD36‐mediated oxLDL uptake

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: CD5L;    Spα;    macrophage;    atherosclerosis;    apoptosis;   

DOI  :  10.1189/jlb.1212660

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

AIMisexpressedbymacrophagesinresponsetoagonistsofthenuclearreceptorsLXR/RXR.Inmice,itactsasanatherogenicfactorbyprotectingmacrophagesfromtheapoptoticeffectsofoxidizedlipids.Inhumans,itisdetectedinatheroscleroticlesions,butnorolerelatedtoatherosclerosishasbeenreported.ThisstudyaimedtoinvestigatewhethertheroleofhAIMextendsbeyondinhibitingoxidizedlipid‐inducedapoptosis.Toaccomplishthisgoal,functionalanalysiswithhumanmonocyticTHP1cellsandmacrophagesdifferentiatedfromperipheralbloodmonocyteswereperformed.ItwasfoundthathAIMreducedoxLDL‐inducedmacrophageapoptosisandincreasedmacrophageadhesiontoendothelialICAM‐1byenhancingLFA‐1expression.Furthermore,hAIMincreasedfoamcellformation,asshownbyOilRedOandNileRedstaining,aswellasquantificationofcholesterolcontent.Thiswasnotaresultofdecreasedreversecholesteroltransport,ashAIMdidnotaffecttheeffluxsignificantlyfrom[3H]Cholesterol‐ladenmacrophagesdrivenbyplasma,apoA‐I,orHDL2acceptors.Rather,flowcytometrystudiesindicatedthathAIMincreasedmacrophageendocytosisoffluorescentoxLDL,whichcorrelatedwithanincreaseintheexpressionoftheoxLDLRCD36.Moreover,hAIMboundtooxLDLinELISAandenhancedthecapacityofHEK‐293cellsexpressingCD36toendocytoseoxLDL,asstudiedusingimmunofluorescencemicroscopy,suggestingthathAIMservestofacilitateCD36‐mediateduptakeofoxLDL.OurdatarepresentthefirstevidencethathAIMisinvolvedinmacrophagesurvival,adhesion,andfoamcellformationandsuggestasignificantcontributiontoatherosclerosis‐relatedmechanismsinthemacrophage...

【 授权许可】

CC BY