Mechanisms of Vascular Damage by Hemorrhagic Snake Venom Metalloproteinases Tissue Distribution and In Situ Hydrolysis 英文参考文献.docVIP

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Mechanisms of Vascular Damage by Hemorrhagic Snake Venom Metalloproteinases Tissue Distribution and In Situ Hydrolysis 英文参考文献.doc

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Mechanisms of Vascular Damage by Hemorrhagic Snake Venom Metalloproteinases Tissue Distribution and In Situ Hydrolysis 英文参考文献

MechanismsofVascularDamagebyHemorrhagicSnake VenomMetalloproteinases:TissueDistributionandIn SituHydrolysis CristianiBaldo1,ColinJamora2,NormaYamanouye3,TelmaM.Zorn4,AnaM.Moura-da-Silva1* 1Laborato′riodeImunopatologia,InstitutoButantan,Sa?oPaulo,Sa?oPaulo,Brasil,2SectionofCellandDevelopmentalBiology,DivisionofBiologicalSciences,University ofCaliforniaSanDiego,LaJolla,California,UnitedStatesofAmerica, 3Laborato′riodeFarmacologia,InstitutoButantan,Sa?o Paulo,Sa?o Paulo,Brasil,4Laborato′rioda BiologiadaReproduc?a?o eMatrizExtracelular,InstitutodeCie?nciasBiome′dicas,USP,Sa?o Paulo,Sa?o Paulo,Brasil Abstract Background:EnvenomingbyvipersnakesconstitutesanimportantpublichealthprobleminBrazilandotherdeveloping countries.Localhemorrhageisanimportantsymptomoftheseaccidentsandiscorrelatedwiththeactionofsnakevenom metalloproteinases(SVMPs).Thedegradationofvascularbasementmembranehasbeenproposedasakeyeventforthe capillaryvesseldisruption.However,SVMPsthatpresentsimilarcatalyticactivitytowardsextracellularmatrixproteinsdiffer intheirhemorrhagicactivity,suggestingthatothermechanismsmightbecontributingtotheaccumulationofSVMPsatthe snakebiteareaallowingcapillarydisruption. Methodology/PrincipalFindings:Inthiswork,wecomparedthetissuedistributionanddegradationofextracellularmatrix proteinsinducedbyjararhagin(highlyhemorrhagicSVMP)andBnP1(weaklyhemorrhagicSVMP)usingthemouseskinas experimental model. Jararhagin induced strong hemorrhage accompanied by hydrolysis of collagen fibers in the hypodermisandamarkeddegradationoftypeIVcollagenatthevascularbasementmembrane.Incontrast,BnP1induced onlyamildhemorrhageanddidnotdisruptcollagenfibersortype IVcollagen.Injection ofAlexa488-labeledjararhagin revealedfluorescentstainingaroundcapillaryvesselsandco-localizationwithbasementmembranetypeIVcollagen.The same distribution pattern was detected with jararhagin-C (disintegrin-like/cysteine-rich domains of jararhagin). In opposition,BnP1didnotaccumulateinthetissues. Conclusio