Protease-activated receptor-1 impairs host defense in murine pneumococcal pneumonia a controlled laboratory study 英文参考文献.docVIP

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Protease-activated receptor-1 impairs host defense in murine pneumococcal pneumonia a controlled laboratory study 英文参考文献.doc

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Protease-activated receptor-1 impairs host defense in murine pneumococcal pneumonia a controlled laboratory study 英文参考文献

Schoutenetal.CriticalCare2012,16:R238 /content/16/6/R238 RESEARCH OpenAccess Protease-activatedreceptor-1impairshost defenseinmurinepneumococcalpneumonia: acontrolledlaboratorystudy MarcelSchouten1,2*,Cornelisvan’tVeer1,2,JorisJTHRoelofs3,MarcelLevi4andTomvanderPoll1,2,5 Abstract Introduction:Streptococcuspneumoniaeisthemostcommoncausativepathogenincommunity-acquired pneumonia.Protease-activatedreceptor-1(PAR-1)isexpressedbymultiplecelltypespresentinthelungsandcan beactivatedbyvariousproteasesgeneratedduringacuteinflammation.ThecellulareffectofPAR-1activation partiallydependsonthespecificproteaseinvolved.WeheredeterminedtheroleofPAR-1inthehostresponse duringmurinepneumococcalpneumonia. Methods:Wild-type(WT)andPAR-1knockout(KO)micewereinfectedintranasallywithviableS.pneumoniaeand observedinasurvivalstudyoreuthanizedat6,24or48hoursofinfection. Results:PAR-1KOmicehadabettersurvivalearlyafterinfectioncomparedtoWTmice.Moreover,PAR-1KOmicehad lowerbacterialloadsinlungsandbloodat24hoursandinspleenandliverat48hoursafterinfection.Thisfavorable responsewasaccompaniedbylowerlunghistopathologyscoresandlessneutrophilinfluxinPAR-1KOmice. Conclusion:PAR-1impairshostdefenseduringmurinepneumococcalpneumonia. Introduction involvedinthecoagulationsystem.Intriguingly, activa- Streptococcus (S.) pneumoniae orthe pneumococcus is tion of PAR-1 can result in opposite cellular effects the number one causative pathogen in community- depending on the protease involved in its proteolytic acquired pneumonia (CAP) [1]. CAP is an important cleavage: for example high concentrations of thrombin causeofsepsis:inarecentlargesepsistrial35.6%ofthe cancausebarrierdisruptiveeffectsonvascularendothe- patientssufferedfromsevereCAP,withthepneumococ- liumviaactivationofPAR-1,whereastheanticoagulant cus being the most frequent cause [2]. Worldwide proteinactivatedproteinC(APC)exertsbarrierprotec- S.pneumoniaeisresponsibleforapproximatelytenmil- tiveandanti-inflammatoryeffectsviathesamer