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Schistosoma

By Walter Myers,2014-07-19 00:01
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SchistosomaSchist

    Schistosoma

ChineseMedicalJournal2004;117(6):947949?947?

    ;concomitantimmunity

    ;hmentofamousemelthatdemonstrates

    ;HELi何立,YIXin.yuan易新元,JIANGMingsen蒋明森,ZENGXianfang曾宪

    ,OUYANGLi欧阳理

    ;andLarryMcReynolds

    ;Keywords:Schistosoma~tponicum?motlsemodel’concomitantimmunity

    ;Concomitantimmunitytoschistosomereinfectioninvivo ;isgenerallythoughttobetheimmuneresponseinduced ;byandrelyingonlivingadultworms.However.a ;fewauthors,havesuggestedthatthemechanismof ;resistancemayberelatedtothehepaticpathologycaused ;bytheprimaryinfection.Thevascularpathologymight ;enablethechallengeschistosomulatoescapefromthe ;hepaticportalsystem,thuspreventingnormalparasite ;sequestrationandmaturationintheliver.

    ;Phenoloxidasehasbeenimplicatedintheprocessof ;eggshellformation.Wehypothesizedthatallylthiourea ;(ATU),themosteffectivephenoloxidaseinhibitor,may ;blocktheformationofSchistosomaonum(S.J) ;eggshel1.Herewereporttheestablishmentofanovel ;modelfNM)basedonATUabbreviatedinfectionthat ;canbeusedtoexploretherealmechanismofimmunityto ;reinfectionwithS.japonicum.

    ;MTHoDS

    ;Establishmentofanewmousemodel

    ;ThirtyBALB/cmicewererandomlydividedintotwo ;groups:experimentalgroupandcontrolgroup.Allofthe ;micewereexposedto40(inexperiment1)or20(in ;experiment2)cercariae.Twentytwodayspostinfection,

    ;miceintheexperimentalgroupwereintraperitoneaUy ;injectedwithallylthioureaatadoseof300mr,/kgevery ;otherday.Twoofthemiceweretreatedatadoseof200 ;mg/kg.Miceinthecontrolgroupwerenottreatedwith ;allylthiourea.

    ;Effectsofallylthioureaonparasites/eggs ;Onday42afterinfection.allthemiceweresacrificed. ;Thecontentoftheuterusoffemaleschistosomeswas ;examined.Eggsinthehostliverwerecountedto

    ;calculatelivereggspergram(LEPG).Theeggsinthe ;uteruswerealsocounted.Someeggswerethenexamined ;usingascanningelectronmicroscope.

    ;Pathologicalchangesinhostliver

    ;Theliverwasremovedfromeachmouseandasmall ;portionwasfixedinformalsalineandembeddedinwax. ;FivemthicksectionswerecutsuccessivelyandHE ;stained.Thelivergranulomadiametersandareasof16 ;lesionsweremeasuredwithanocularmicrometer. ;Statisticalsignificancewascalculatedusingttest. ;ParasiteChallenge

    ;BALB/cmiceinGroupsAandBwereeachexposedto ;40(experiment1)or20(xperiment2)cercariae.Six ;weeksafterprima~infection,micewerechallengedwith ;thesamenumberofcercariae.MiceingroupAwere ;injectedwithATUat300mr,/kgeveryotherday ;beginning22daysafterprimaryinfection.GroupBmice ;werenottreatedwithATU.GroupCmicewereonly ;subiectedtotheprima~infection,andGroupDwere ;onlysubiectedtothechallengeinfectioninorderto ;establishthechallengecontro1.Twentydays(experiment ;1)or35days(experiment2)afterthechallenge ;infection.allthemiceweresacrificedandperfusedwith ;normalsaline.Thepercentagereductioninseverityofthe ;chaUengeinfectionwascalculatedaccordingtothe ;followingfornlula:Percentagereduction=1(mean

    ;numberofwormsingroupA/Bmeannumberofworms

    ;ingroupC)/meannumberofwormsingroupD.

    ;DepartmentofPathogenBiology,WuhanUniversityMedicalSchool, ;Wuhan430071(HeLandJiangMS)

    ;DepartmentofPathogenBiology,CentralSouthUniversityXiangya ;MedicalSchool,Changsha410078,China(YiXY,ZengXFand ;OuyaagL)

    ;NewEnglandBiolabs,Inc.,MA01915,USA(McReynoldsL) ;Correspondenceto:Dr.YiXinyuan,DepartmentofPathogen

    ;Biology,CentralSouthUniversity~angyaMedicalSchool, ;Changsha410078,China(Tel:86-731-4498311.Fax:86-731

    ;4498311.Email:xinyuanyi555@yahoo.corn.cn) ;ThisprojectwassupportedbyagrantfromtheNationalNatural ;ScienceFoundationofChina(No.30240074).

    ;

    ;?

    ;948?ChineseMedicalJournal2004;”7(6):947—949

    ;RESULTS

;Inhibitionofeggformationinvivo

    ;WhenmicewereintraperitoneallyinjectedwithATU ;everyotherdayatadoseof300mg/kg,theuteriofthe ;S.J.WO1TflSwerefoundtobefilledwithaquantityof ;sandlikematter,indicatingthattheformationof ;eggshellswascompletelyinhibited.Whenthedosewas ;loweredto200mg/kg,theinhibitionofeggformationwas ;incomplete.Severalabnormaleggswereobservedatthe ;juxtaootypicsegmentoftheuterus.Scanningelectron ;microscopyshowedthattheeggshadanovalshape,but ;withoutatypicalshellstructure.Thecontourofthe ;vitellinecellswasclearlydemonstrated(datanot ;shown).

    ;Theeggloadintheliverwasalsoexamined.Noeggs ;couldbefoundinlivertissuesuspensionsfrommice ;treatedwithATUatadoseof300mg/kg.whilethe ;LEPGwas4900and13750,respectively,inthetwo ;micetreatedatadoseof200mr,/kgdose.TheLEPGin ;theuntreatedcontrolgroupwas21530?15397. ;Differentliverpathologiesinthetwomodels ;ThepathologicalchangesintheliversofNMmicewere ;alsoexamined.Notypicalegggranulomaswereobserved; ;instead.therewerescatteredfociofinflammatorycell ;infiltrationinthemouselivers.Inthecenterofthefoci. ;therewassomegranularmatterwhichmighthave ;originatedfromvitellinecells.Eosinophilsand ;lymphocyteswerethemajorcomponentsofthe ;surroundinginflammatorycells.However.comparedto ;thegranulomasmeasuring280.2?30.7minaverage ;diameterintheroutinemodel(RM).thenumberofcells ;andtheareaofinflammatoryinflhrationinthefociofthe ;liversofNMmiceweresignificantlySillaller(P<0.011. ;Theaveragediameterofthefociwas191.3?28.6LLm. ;Someofthefociwerecomposedofonlydozensofcells. ;Thelackofmatureeggs,togetherwithpalliativehepatic ;pathology.indicatedthesuccessfulestablishmentofa ;newmousemodelofschistosomeinfection.

    ;Isistancetoreinfectioninthenewmodel

    ;Inordertoexaminetheresistancetoreinfectioninthe ;newmodel,wechallengedtheATU.treatedmicewith ;S.cercariaesixweeksafterprimaryinfection. ;ComparedwithRMmice,NMmiceshowedasignificantly ;higherprotectionagainstreinfection(Table1). ;ToruleouttheeffectofATUonthechallengeinfection,

    ;wecomparedtherateofadultworlnrecoveryfroman ;ATUtreatedgroup(E)andanuntreatedgroup(D). ;Theresultsshowedthatnodifierenceexistedbetweenthe ;twogroups(Table2)

    ;Table1.Comparisonofwornqnumbemrecoveredfrom ;differentgroups

    ;GroupA:AUTtreated,P+C;GroupB:Untreated,P+C;GroupC: ;Untreated,P;GroupD:Untreated,C.P:Primaryinfection;C:Challenge

    ;infection.ThenumberofcercariaeusedforpHmary/challengeinfectionswas

    ;40inexperiment1and20inexperiment2.Thesacrificedatewas20days ;postchallengeforexpe~ment1and35dayspostchallengeforexperiment2. ;}P<0.05vsgroupAineachexperimenL

    ;Table2.ComparisonofwornqnumberrecoveredinATUtreated

    ;anduntreatedgroups

    ;}P>0.05vsgroupD

    ;DIsCUSSION

    ;Takentogether,ourfindingsindicatethatwehave ;successfullyestablishedanewconcomitantimmunity ;modelinwhichseveraldistinctcharacteristicscanbe ;observed.First,theinhibitionofeggproduction ;eliminatestheexcretionofsolubleeggantigens(SEA) ;and,hence,theproductionofblockingantibodiesinNM ;mice,whichmayexplaintheenhancementof

    ;resistancetoreinfection.Second,comparedwiththe ;irradiatedvaccinemode1.whichisdependenton ;attenuatedcercariae,theprotectionagainstreinfection ;duetoconcomitantimmunityiSdependentontheliving ;adultwormsinNMmice.nlird.thehepaticpathologyis ;muchweakerinNMmicethaninRMmice.thoughthe ;granularmatteroriginatingfromthevitellinecellsstill ;stimulatessmallfociofinflammatorycellinfihration. ;whichdoesnotaffectthelivervascularstructureinNM ;Insummary,ourresultsstronglysupportthehypothesis ;firstproposedbySmithersandTerryin1969thatthe ;resistanceofthedefinitivehosttoschistosomereinfection ;isrelatedtoconcommitantimmunityinducedbyadult ;worlnsinvivo,whichnotaffecttheestablishedadult ;

    ;ChineseMedicalJournal2004;117(6):947949949?

    ;WOFInSbutdoesaffectreinfectionwiththeparasiteinthe ;larvalstage.

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    ;(ReceivedFebruary16,2004)

    ;本文编辑:沈锡宾

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