Electric fields are novel determinants of human macrophage functions

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

关键词: direct current;    phagocytosis;    migration;    cytokines;    wound repair;   

DOI  :  10.1189/jlb.3A0815-390R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Macrophagesarekeycellsininflammationandrepair,andtheiractivityrequirescloseregulation.Thecharacterizationofcuescoordinatingmacrophagefunctionhasfocusedonbiologicandsolublemediators,withlittleknownabouttheirresponsestophysicalstimuli,suchastheelectricalfieldsthataregeneratednaturallyininjuredtissueandwhichacceleratewoundhealing.Toaddressthisgapinunderstanding,wetestedhowpropertiesofhumanmonocyte‐derivedmacrophagesareregulatedbyappliedelectricalfields,similarinstrengthstothoseestablishednaturally.Withtheuseoflive‐cellvideomicroscopy,weshowthatmacrophagemigrationisdirectedanodallybyelectricalfieldsaslowas5mV/mmandiselectricalfieldstrengthdependent,witheffectspeaking∼300mV/mm.Monocytes,asmacrophageprecursors,migrateintheopposite,cathodaldirection.Strikingly,weshowforthefirsttimethatelectricalfieldssignificantlyenhancemacrophagephagocyticuptakeofavarietyoftargets,includingcarboxylatebeads,apoptoticneutrophils,andthenominalopportunistpathogenCandidaalbicans,whichengagedifferentclassesofsurfacereceptors.Theseelectricalfield‐inducedfunctionalchangesareaccompaniedbyclusteringofphagocyticreceptors,enhancedPI3KandERKactivation,mobilizationofintracellularcalcium,andactinpolarization.Electricalfieldsalsomodulatecytokineproductionselectivelyandcanaugmentsomeeffectsofconventionalpolarizingstimulioncytokinesecretion.Takentogether,electricalsignalshavebeenidentifiedasmajorcontributorstothecoordinationandregulationofimportanthumanmacrophagefunctions,includingthoseessentialformicrobialclearanceandhealing.Ourresultsopenupanewareaofresearchintoeffectsofnaturallyoccurringandclinicallyappliedelectricalfieldsinconditionswheremacrophageactivityiscritical...

【 授权许可】

CC BY