Expression and role of a2 vacuolar‐ATPase (a2V) in trafficking of human neutrophil granules and exocytosis

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

关键词: MPO;    elastase;    pH;    VOa isoforms;    fusion;   

DOI  :  10.1189/jlb.3A1214-620RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Neutrophilskillmicroorganismsbyinducingexocytosisofgranuleswithantibacterialproperties.Fourisoformsofthe“a”subunitofV‐ATPase—a1V,a2V,a3V,anda4V—havebeenidentified.a2Visexpressedinwhitebloodcells,thatis,onthesurfaceofmonocytesoractivatedlymphocytes.Neutrophilassociated‐a2Vwasfoundonmembranesofprimary(azurophilic)granulesandlessoftenonsecondary(specific)granules,tertiary(gelatinasegranules),andsecretoryvesicles.However,itwasnotfoundonthesurfaceofrestingneutrophils.Followingstimulationofneutrophils,primarygranulescontaininga2VaswellasCD63translocatedtothesurfaceofthecellbecauseofexocytosis.a2Vwasalsofoundonthecellsurfacewhentheneutrophilswereincubatedinammoniumchloridebuffer(pH7.4)aweakbase.TheintracellularpH(cytosol)becamealkalinewithin5minafterstimulation,andthepHincreasedfrom7.2to7.8;thispHchangecorrelatedwithintragranularacidificationoftheneutrophilgranules.Upontranslocationandexocytosis,a2Vonthemembraneofprimarygranulesremainedonthecellsurface,butmyeloperoxidasewassecreted.V‐ATPasemayhavearoleinthefusionofthegranulemembranewiththecellsurfacemembranebeforeexocytosis.Thesefindingssuggestthatthegranule‐associateda2VisoformhasaroleinmaintainingapHgradientwithinthecellbetweenthecytosolandgranulesinneutrophilsandalsoinfusionbetweenthesurfaceandthegranulesbeforeexocytosis.Becausea2Visnotfoundonthesurfaceofrestingneutrophils,surfacea2Vmaybeusefulasabiomarkerforactivatedneutrophils...

【 授权许可】

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