Lipid rafts couple class A scavenger receptors to phospholipase A2 activation during macrophage adhesion

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

关键词: prostaglandin;    arachidonic acid;    signaling;    cholesterol;    membrane domains;    receptor localization;   

DOI  :  10.1189/jlb.2A0414-214R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

SR‐AmediatedmacrophageadhesiontomodifiedECMproteinsinaprocessthatinvolvesphysicalattachmentofSR‐AtomodifiedECMandactivationofLyn‐PI3KandPLA2‐12/15‐lipoxygenasesignalingpathways.Structurally,SR‐A‐mediatedcelladhesionrequiresa6‐aamembrane‐proximalcytoplasmicmotif.However,themechanismthatcouplesSR‐A‐mediatedadhesiontoactivationofthesedistinctsignalingpathwaysisnotknown.Forotheradhesionreceptors,includingintegrins,localizationincholesterol‐richLRsisanimportantmechanismforcouplingthereceptorwiththeactivationofspecificsignalingpathways.WehypothesizedthatSR‐A‐mediatedmacrophageadhesionmightalsoinvolveLRs.OurresultsdemonstratethatSR‐AisenrichedinLRsinHEKcellsthatheterologouslyexpressSR‐Aandinmacrophagesthatendogenouslyexpressedthereceptor.WefurthershowthatatruncatedSR‐Aconstruct(SR‐AΔ1–49),whichmediatescelladhesionbutnotligandinternalization,isalsoenrichedinLRs,suggestinganassociationbetweenLRsandSR‐A‐dependentcelladhesion.Toexaminethisassociationmoredirectly,weusedthecholesterolchelatorMβCDtodepletecholesterolanddisruptLRfunction.WefoundthatcholesteroldepletionsignificantlydecreasedSR‐A‐mediatedmacrophageadhesion.WefurthershowthatdecreasedSR‐A‐dependentmacrophageadhesionfollowingcholesteroldepletionresultsfromtheinhibitionofPLA2butnotPI3Kactivation.Overall,ourresultsdemonstrateanimportantroleforLRsinselectivelycouplingSR‐AwithPLA2activationduringmacrophageadhesion...

【 授权许可】

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