Granulocyte functions are independent of arginine availability

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

关键词: innate immunity;    immunosuppression;    arginase;    neutrophil;   

DOI  :  10.1189/jlb.3AB0214-082R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Argininedepletionviamyeloidcellarginaseiscriticallyinvolvedinsuppressionoftheadaptiveimmunesystemduringcancerorchronicinflammation.Ontheotherhand,argininedepletionisbeingdevelopedasanovelanti‐tumormetabolicstrategytodeprivearginine‐auxotrophiccancercellsofthisaminoacid.Inhumanimmunecells,arginaseismainlyexpressedconstitutivelyinPMNs.WethereforepurifiedhumanprimaryPMNsfromhealthydonorsandanalyzedPMNfunctionasthemaininnateeffectorcellandarginaseproducerinthecontextofargininedeficiency.WedemonstratethathumanPMNviability,activation‐inducedIL‐8synthesis,chemotaxis,phagocytosis,generationofROS,andfungicidalactivityarenotimpairedbytheabsenceofarginineinvitro.Also,profoundpharmacologicalargininedepletioninvivoviaADI‐PEG20didnotinhibitPMNfunctionsinamousemodelofpulmonaryinvasiveaspergillosis;PMNinvasionintothelung,activation,andsuccessfulPMN‐dependentclearanceofAspergillusfumigatusandsurvivalofmicewerenotimpaired.Thesenovelfindingsaddtoabetterunderstandingofimmunityduringinflammation‐associatedargininedepletionandarealsoimportantforthedevelopmentoftherapeuticargininedepletionasanti‐metabolictumortherapy...

【 授权许可】

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