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1、Hanaokaetal.RespiratoryResearch2010,11:179http://respiratory-research.com/content/11/1/179RESEARCHOpenAccessImmunomodulatorystrategiespreventthedevelopmentofautoimmuneemphysema12131MasayukiHanaoka,MarkRNicolls,AndrewPFontenot,DonatasKraskauskas,DouglasGMack,11313AdelheidKra
2、tzer,JonasSalys,VitaKraskauskiene,NanaBurns,NorbertFVoelkel,1*LaimuteTaraseviciene-StewartAbstractBackground:Thepresenceofanti-endothelialcellantibodiesandpathogenicTcellsmayreflectanautoimmunecomponentinthepathogenesisofemphysema.Whetherimmunemodulatorystrategiescanprotect
3、againstthedevelopmentofemphysemaisnotknown.Methods:SpragueDawleyratswereimmunizedwithhumanumbilicalveinendothelialcells(HUVEC)toinduceautoimmuneemphysemaandtreatedwithintrathymicHUVEC-injectionandpristane.Measurementsofalveolarairspaceenlargement,cytokinelevels,immunohistoc
4、hemical,westernblotanalysis,andTcellrepertoireofthelungtissuewereperformed.Results:TheimmunomodulatorystrategiesprotectedlungsagainstcelldeathasdemonstratedbyreducednumbersofTUNELandactivecaspase-3positivecellsandreducedlevelsofactivecaspase-3,whencomparedwithlungsfromHUVEC
5、-immunizedrats.Immunomodulatorystrategiesalsosuppressedanti-endothelialantibodyproductionandpreservedCNTF,IL-1alphaandVEGFlevels.TheimmunedeviationeffectsoftheintrathymicHUVEC-injectionwereassociatedwithanexpansionofCD4+CD25+Foxp3+regulatoryTcells.Pristanetreatmentdecreased
6、theproportionofTcellsexpressingreceptorbeta-chain,Vb16.1inthelungtissue.Conclusions:OurdatademonstratethatinterventionsclassicallyemployedtoinducecentralTcelltolerance(thymicinoculationofantigen)ortoactivateinnateimmuneresponses(pristanetreatment)canpreventthedevelopmentofa
7、utoimmuneemphysema.Backgroundsmokingcessation[9-12].RecentlyLeeandco-workersItisnowincreasinglyrecognizedthatchronicobstruc-demonstratedanti-elastinautoantibodiesinpatientstivepulmonarydisease(COPD)/emphysemapresentswithtobaccosmoking-inducedemphysema[13].clinicallyasasyndr
8、omewithpulmonaryandextra-Autoimmunediseasesresultfromthepropagationofpulmonarymani