Chronic alcohol ingestion modulates hepatic macrophage populations and functions in mice

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

关键词: M1 macrophages;    M2 macrophages;    Kupffer cells;   

DOI  :  10.1189/jlb.6A0114-004RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

HepaticMacs,consistingofresidentKCsandinfiltratingmonocytes/IMs,arethoughttoplayanimportantroleinthepathogenesisofALD.PreviousworkhasfocusedonKCsorstudiedhepaticMacsasonecellpopulation.TheaimofthecurrentstudyistodistinguishIMsfromKCsandtocomparetheirphenotypesandfunctions.Weshowherethata4‐weekethanolfeedingofC57BL/6JmicecausesrecruitmentofIMsintotheliver.KCsandIMscanbedistinguishedbasedontheirdifferentialexpressionofF4/80andCD11b.IMscanbedividedfurtherintotwosubsetsbasedontheirdifferentialexpressionofLy6C.KCsandtwosubsetsofIMswereseparatelypurifiedbyFACS.ThephagocytosisabilitiesandtheexpressionprofilesofgenesrelatedtovariousfunctionswerecomparedamongdifferentpopulationsofhepaticMacs.Ly6ClowIMsexhibitananti‐inflammatoryandtissue‐protectivephenotype;incontrast,Ly6ChiIMsexhibitaproinflammatory,tissue‐damagingphenotype.TheratioofLy6Chi/Ly6Clowincreaseswhenmicechronicallyfedethanolwerebinged,whichsignificantlyenhancedliverinjury.Moreover,uponphagocytosisofapoptotichepatocytes,Ly6ChiIMsswitchtoLy6ClowIMs.Takentogether,chronicethanolfeedinginducestherecruitmentoftwosubsetsofhepaticIMs,whichplaydifferentorevenoppositerolesinregulatingliverinflammationandrepair.ThesefindingsmaynotonlyincreaseourunderstandingofthecomplexfunctionsofMacsinthepathogenesisofALDbutalsohelpustoidentifynoveltherapeutictargetsforthetreatmentofthisdisease...

【 授权许可】

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