Proteomic Analysis of Skin Invasion by Blood Fluke Larvae 英文参考文献.docVIP

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Proteomic Analysis of Skin Invasion by Blood Fluke Larvae 英文参考文献.doc

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Proteomic Analysis of Skin Invasion by Blood Fluke Larvae 英文参考文献

ProteomicAnalysisofSkinInvasionbyBloodFluke Larvae ElizabethHansell1*,SimonBraschi1,KatalinF.Medzihradszky2,MohammedSajid1,MoumitaDebnath1, JessicaIngram1,K.C.Lim1,JamesH.McKerrow1 1SandlerCenter,CaliforniaInstituteforQuantitativeBiosciences(QB3),UniversityofCalifornia,SanFrancisco,California,UnitedStatesofAmerica,2MassSpectrometry Facility,DepartmentofPharmaceuticalChemistry,SchoolofPharmacy,UniversityofCalifornia,SanFrancisco,California,UnitedStatesofAmerica Abstract Background: During invasion of human skin by schistosome blood fluke larvae (cercariae), a multicellular organism breachestheepidermis,basementmembrane,anddermalbarriersofskin.Tobetterunderstandthepathobiologyofthis initialeventinschistosomeinfection,aproteomeanalysisofhumanskinwascarriedoutfollowinginvasionbycercariaeof Schistosomamansoni. MethodologyandResults:Humanskinsampleswereexposedtocercariaeforone-halfhourtotwohours.Controlswere exposedtowaterusedtocollectcercariaeinanidenticalmanner,andpuncturedtosimulatecercarialtunnels.Fluidfrom both control and experimental samples was analyzed by LC/MS/MS using a linear ion trap in ‘‘triple play’’ mode. The coexistenceofproteinsreleasedbycercariaeandhostskinproteinsfromepidermisandbasementmembraneconfirmed thatcercarialtunnelsinskinweresampled.Amongtheabundantproteinssecretedbycercariaewasthecercarialprotease that has been implicated in degradation of host proteins, secreted proteins proposed to mediate immune invasion by larvae,andproteinsimplicatedinprotectionofparasitesagainstoxidativestress.Componentsoftheschistosomesurface tegument,previouslyidentifiedwithimmuneserum,werealsoreleased.Bothlysisandapoptosisofepidermalcellstook placeduringcercarialinvasionoftheepidermis.Componentsoflysedepidermalcells,includingdesmosomeproteinswhich link cells in the stratum granulosum and stratum spinosum, were identified. While macrophage-derived proteins were present, no mast cell or lymphocyte cytokines were identified. There were, however, abundant immunoglobuli