Macrophage uptake and accumulation of folates are polarization‐dependent in vitro and in vivo and are regulated by activin A

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

关键词: macrophage metabolism;    folate metabolism;    folate receptor beta;    folate transporters;   

DOI  :  10.1189/jlb.0613345

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

VitaminB9,commonlyknownasfolate,isanessentialcofactorforone‐carbonmetabolismthatenterscellsthroughthreemajorspecializedtransportermolecules(RFC,FR,andPCFT),whichdifferinexpressionpattern,affinityforsubstrate,andligand‐bindingpHdependency.Wenowreportthattheexpressionofthefolatetransportersdiffersbetweenmacrophagesubtypesandexplainsthehigheraccumulationof5‐MTHF—themajorfolateformfoundinserum—inM2macrophagesinvitroandinvivo.M1macrophagesdisplayahigherexpressionofRFC,whereasFRβandPCFTarepreferentiallyexpressedbyanti‐inflammatoryandhomeostaticM2macrophages.Thesedifferencesarealsoseeninmacrophagesfromnormaltissuesinvolvedinfolatetransit(placenta,liver,colon)andinflamedtissues(ulcerativecolitis,RA),asM2‐likemacrophagesfromnormaltissuesexpressFRβandPCFT,whereasTNF‐α‐expressingM1macrophagesfrominflamedtissuesareRFC+.Besides,weprovideevidencesthatactivinAisacriticalfactorcontrollingthesetoffolatetransportersinmacrophages,asitdown‐regulatesFRβ,up‐regulatesRFCexpression,andmodulates5‐MTHFuptake.Alloftheseexperimentssupportthenotionthatfolatehandlingisdependentonthestageofmacrophagepolarization...

【 授权许可】

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