Exocytosis of azurophil and arginase 1‐containing granules by activated polymorphonuclear neutrophils is required to inhibit T lymphocyte proliferation

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

关键词: granulocytes;    T cell proliferation;    arginase;    granules;   

DOI  :  10.1189/jlb.1109737

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

ARG1,expressedbyhumanPMNs,inhibitsTcellproliferationbydepletingextracellularl‐arginine.Here,wereportthatARG1,releasedfromgelatinasegranulesbyPMNs,isinactiveatphysiologicalpHunlessactivatedbyfactor(s)storedinazurophilgranules.WhereasARG1exocytosiswasinducedbyTNF‐αorionomycin,onlythelattermediatedthereleaseofbothgranules,resultinginextracellularARGenzymeactivityatphysiologicalpH.Furthermore,afterfractionationofthedifferentclassesofgranules,onlythemixtureofgelatinaseandazurophilgranulesresultedinARG1activityatphysiologicalpH.TheuseofproteaseinhibitorsindicatedtheinvolvementofaPMSF‐andleupeptin‐susceptibleserineproteaseinARG1processingandactivation.Finally,thesupernatantofviablePMNsundergoingfrustratedphagocytosis,whichmediatesgelatinaseandazurophilgranulerelease,inhibitedTcellproliferationthroughARG‐dependentmechanisms.Invivo,highARG1concentrationsandincreasedARGenzymeactivity,sufficienttoinhibitTcellproliferation,wereobservedinsynovialfluidsfromRA.ThesefindingssuggestthatPMNs,recruitedatsitesofimmunecomplexdeposition,induceARG1‐dependentimmunesuppressionthroughconcomitantexocytosisofgelatinaseandazurophilgranules...

【 授权许可】

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