Antibody-Dependent Transplacental Transfer of Malaria Blood-Stage Antigen Using a Human Ex Vivo Placental Perfusion Model 英文参考文献.docVIP

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Antibody-Dependent Transplacental Transfer of Malaria Blood-Stage Antigen Using a Human Ex Vivo Placental Perfusion Model 英文参考文献.doc

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Antibody-Dependent Transplacental Transfer of Malaria Blood-Stage Antigen Using a Human Ex Vivo Placental Perfusion Model 英文参考文献

Antibody-DependentTransplacentalTransferofMalaria Blood-StageAntigenUsingaHumanExVivoPlacental PerfusionModel KarenMay1,MarkusGrube1,InduMalhotra3,CaroleA.Long4,SanjaySingh4,KishorMandaliya5 ,Werner Siegmund1,ChristophFusch2,HenningSchneider6,ChristopherL.King3,7* 1DepartmentofPharmacology,ErnstMoritzArndtUniversityofGreifswald,Greifswald,Germany,2DepartmentofPediatrics,ErnstMoritzArndtUniversityofGreifswald, Greifswald,Germany,3CenterforGlobalHealthandDiseases,CaseWesternReserveUniversity,Cleveland,Ohio,UnitedStatesofAmerica,4MalariaVaccineDevelopment UnitandLaboratoryofMalariaandVectorResearch,NationalInstitutesofHealth,Bethesda,Maryland,UnitedStatesofAmerica,5PathologyServices,KenyanMinistryof Health, Mombasa General Hospital, Mombasa, Kenya, 6Departmentof Obstetrics and Gynecology, University ofBerne, Berne,Switzerland, 7Louis B. Stokes Veterans AffairsMedicalCenter,Cleveland,Ohio,UnitedStatesofAmerica Abstract Prenatalexposuretoallergensorantigensreleasedbyinfectionsduringpregnancycanstimulateanimmuneresponseor induceimmunoregulatorynetworksinthefetusaffectingsusceptibilitytoinfectionanddiseaselaterinlife.Howantigen crossesfromthematernaltofetalenvironmentispoorlyunderstood.Onehypothesisisthattransplacentalantigentransfer occurs as immune complexes, via receptor-mediated transport across the syncytiotrophoblastic membrane and endothelium of vessels in fetal villi. This hypothesis has never been directly tested. Here we studied Plasmodium falciparummerozoitesurfaceprotein1(MSP1)thatisreleaseduponerythrocyteinvasion.WefoundMSP1incordblood from a third of newborns of malaria-infected women and in .90% following treatment with acid dissociation demonstrating MSP1 immune complexes. Using an ex vivo human placental model that dually perfuses a placental cotyledon with independent maternal and fetal circuits, immune-complexed MSP1 transferred from maternal to fetal circulation.MSP1aloneorwithnon-immuneplasmadidnottransfer;pre-incubationwithhumanplasmacontaininga