Rac2 is required for the formation of neutrophil extracellular traps

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

关键词: NET;    NADPH oxidase;    nitric oxide synthase;    small GTPase;    ROS;    NO;   

DOI  :  10.1189/jlb.1010549

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Neutrophilsplayacriticalroleasafirstlineofdefenseagainstinvadingpathogens.Recently,anewdefensestrategyofneutrophilswasdescribed,inwhichpathogensaretrappedandkilledbyNETs.However,theexactunderlyingmechanismsleadingtotheformationofNETsremainelusive.Here,weexploredtheroleoftheRacsmallGTPasesintheformationofNETsusingneutrophilsthatlackRac1,Rac2,orbothisoforms.EfficientNETformationwasobservedinWTandRac1nullneutrophils.Incontrast,NETformationwasmarkedlyimpairedincellslackingRac2orbothRac2andRac1.ThedefectinNETformationinRac2nullcellswasrescuedbyexogenousROSsources,suggestingthatRac2‐mediatedROSgenerationisrequiredforNETformation.Inaddition,weassessedtheroleofNOinNETformationinmouseneutrophils.BlockingNOproductionwiththeNOSinhibitorL‐NAMEsignificantlyreducedNETformation.Moreover,weshowthatRac2nullcellsproducesignificantlylessNOthanRac1nullcellsortheirWTcounterparts.OurdatasuggestthatRac2isessentialforNETformationviapathwaysinvolvingROSandNO...

【 授权许可】

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