Endothelial damage induced by Shiga toxins delivered by neutrophils during transmigration

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

关键词: hemolytic uremic syndrome;    polymorphonuclear leukocytes;    endothelial cells;    proinflammatory cytokine;    degranulation;   

DOI  :  10.1189/jlb.0709475

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

TheendothelialdamageinducedbyStxrepresentsthemainpathogeniceventintheHUSassociatedwithSTECinfectionsinhumans.Stx,releasedinthegutbybacteria,enterthebloodstreamandaretargetedtorenalendothelia.TheroleofPMNasatoxincarrierhasbeentheobjectofcontroversy.Inthispaper,weconfirmthebindingofStx1toPMN,alsoshowingitsdegranulatingeffectsonfull‐loadedleukocytes,andsupportthecarrierroleofPMNbyusingatwo‐chambertransmigrationdevice,inwhichPMN,loadedinvitrowithdifferentamountsofStx1,transmigratedthroughconfluentmonolayersofendothelialcells,mimickingthetoxin‐inducedrenalendothelialinjury.Stx1wastransferredduringPMNtransmigration,impairingproteinsynthesisandtriggeringproductionofproinflammatorycytokinesinendothelialcells.PMN,carryinglowtoxinamounts,inducedthereleaseofhighlevelsofcytokinesinviableendothelialcells,whereascytokineproductionwasblockedincellschallengedwithPMNfullyloadedwithStxasaresultofanalmosttotalimpairmentoftranslationandoftheactivationoftheapoptoticprogram.Inagreementwithpreviousunexplainedobservationsinanimalmodels,theresultsobtainedwithourexperimentalsettingsuggestthataself‐amplifyingcircletriggeredbylowdosesoftoxinmayleadtotheproductionofproinflammatorymediatorsofrenaldamageinHUS...

【 授权许可】

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