In vivo‐transmigrated human neutrophils are resistant to antiapoptotic stimulation

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

关键词: phagocyte;    granulocyte;    apoptosis;    transmigration;    skin chamber;    exudate;   

DOI  :  10.1189/jlb.0111051

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Neutrophilsrespondtomicrobialinvasionorinjurybytransmigrationfrombloodtotissue.Transmigrationinvolvescellularactivationanddegranulation,resultinginalteredlevelsofsurfacereceptorsandchangedresponsivenesstocertainstimuli.Thus,fundamentalfunctionalchangesareassociatedwithneutrophiltransmigrationfrombloodtotissue.Neutrophilsisolatedfromperipheralbloodspontaneouslyenterapoptosis,aprocessthatcanbeacceleratedordelayedbydifferentpro‐orantiapoptoticfactors.Howtissueneutrophilsthathavetransmigratedinvivoregulatecelldeathispoorlyunderstood.Inthisstudy,invivo‐transmigratedneutrophils(tissueneutrophils)werecollectedusingaskinchambertechniqueandcomparedwithbloodneutrophilsfromthesamedonorswithrespecttoregulationofcelldeath.Skinchamberfluidcontainedavarietyofcytokinesknowntoactivateneutrophilsandregulatetheirlifespan.Freshlypreparedtissueneutrophilshadelevatedactivityofcaspase3/7butwerefullyviable;spontaneouscelldeathafterinvitroculturewasalsosimilarbetweenbloodandtissueneutrophils.Whereasapoptosisofculturedbloodneutrophilswasdelayedbysolubleantiapoptoticfactors(e.g.,TLRligands),tissueneutrophilswerecompletelyresistanttoantiapoptoticstimulation,eventhoughreceptorswerepresentandfunctional.Invitrotransmigrationofbloodneutrophilsintoskinchamberfluiddidnotfullyconferresistancetoantiapoptoticstimulation,indicatingthatablockofantiapoptoticsignalingoccursspecificallyduringinvivotransmigration.Wedescribeanovel,functionalalterationthattakesplaceduringinvivotransmigrationandhighlightsthefactthatlifeanddeathofneutrophilsmayberegulateddifferentlyinbloodandtissue...

【 授权许可】

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