Granulocyte functions are independent of arginine availability

[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...

[学科分类] 生理学

[关键词] innate immunity;immunosuppression;arginase;neutrophil