SOCS3 is a modulator of human macrophage phagocytosis

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

关键词: live‐;    cell imaging;    PI3K;    Rac1;   

DOI  :  10.1189/jlb.3A1215-554RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Suppressorofcytokinesignaling(SOCS)proteinsarerecognizedaskeyfeedbackinhibitorsmodulatingtheinflammatoryactivitiesofmacrophages,butcomparativelylittleisknownaboutwhetherandhowtheyaffectphagocytosis.Here,weevaluatedtheroleofSOCS3indrivingtheinflammatoryphenotypeandphagocyticuptakeofapoptoticcellsbyhumanmacrophagesandthesignalingpathwaysthatarenecessaryforefficientphagocytosis.InM1‐activatedhumanmonocyte‐derivedmacrophages,SOCS3silencing,usingshortinterferingRNAtechnology,resultedinadecreasedexpressionofproinflammatorymarkersandanincreasedexpressionofM2macrophagemarkers.Strikingly,wedemonstratedforthefirsttimethatSOCS3knockdownsignificantlyenhancesthephagocyticcapacityofM1macrophagesforcarboxylate‐modifiedbeadsandapoptoticneutrophils.Withtheuseoflive‐cellvideomicroscopy,weshowedthatSOCS3knockdownradicallyaffectsthetemporaldynamicsofparticleengulfment,enablingmorerapiduptakeofasecondtargetanddelayingpostengulfmentprocessing,asevidencedbydeferredacquisitionofphagosomematurationmarkers.SOCS3knockdownimpactsonphagocytosisthroughincreasedPI3KandRas‐relatedC3botulinumtoxinsubstrate1(Rac1)activity,pathwaysessentialforengulfmentandclearanceofapoptoticcells.EnhancedphagocytosisinSOCS3‐silencedcellswasreversedbypharmacologicalPI3Kinhibition.Furthermore,werevealedthatactinpolymerization,downstreamofPI3K/Rac1activation,wassignificantlyalteredinSOCS3‐silencedcells,providingamechanismfortheirgreaterphagocyticactivity.Thefindingssupportanewmodel,wherebySOCS3notonlyplaysanimportantroleindrivingmacrophageinflammatoryresponsesbutmodulateskeysignalingpathwaysorganizingtheactincytoskeletontoregulatetheefficiencyofphagocyticprocesses...

【 授权许可】

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