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Differential Modulation of ATP-Induced P2X7-Associated Permeabilities to Cations and Anions of Macrophages by Infection with Leishmania amazonensis 英文参考文献.docVIP

Differential Modulation of ATP-Induced P2X7-Associated Permeabilities to Cations and Anions of Macrophages by Infection with Leishmania amazonensis 英文参考文献.doc

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DifferentialModulationofATP-InducedP2X7-Associated PermeabilitiestoCationsandAnionsofMacrophagesby InfectionwithLeishmaniaamazonensis CamilaMarques-da-Silva1,MarianaMartinsChaves1,JulianyColaRodrigues1,SuzanaCorte-Real2, RobsonCoutinho-Silva1*,PedroMuanisPersechini1 1InstitutodeBiofisicaCarlosChagasFilho,UniversidadeFederaldoRiodeJaneiro,RiodeJaneiro,RiodeJaneiro,Brazil,2InstitutoOswaldoCruz,Fundac?a?oOswaldoCruz, RiodeJaneiro,RiodeJaneiro,Brazil Abstract Leishmania and other parasites display several mechanisms to subvert host immune cell function in order to achieve successfulinfection.TheATPreceptorP2X7,anagonist-gatedcationchannelwidelyexpressedinmacrophagesandother cellsoftheimmunesystem,isalsocoupledtoinflammasomeactivation,IL-1betasecretion,productionofreactiveoxygen species,celldeathandtheinductionofthepermeabilizationoftheplasmamembranetomoleculesofupto900Da.P2X7 receptors can function as an effective microbicidal triggering receptor in macrophages infected with several microorganisms including Mycobacteria tuberculosis, Chlamydia and Leishmania. We have previously shown that its expressionisup-regulatedinmacrophagesinfectedwithL.amazonensisandthatinfectedcellsalsodisplayanincreasein P2X7-inducedapoptosisandmembranepermeabilizationtosomeanionicfluorescentdyes.Inanindependentstudywe recently showed that the phenomenon of macrophage membrane permeabilization can involve at least two distinct pathways for cations and anions respectively. Here, we re-addressed the effects of ATP-induced P2X7-associated phenomena in macrophages infected with L.amazonensis and demonstrated that the P2X7-associated dye uptake mechanisms are differentially modulated. While the membrane permeabilization for anionic dyes is up-modulated, as previouslydescribed,theuptakeofcationicdyesisstronglydown-modulated.Theseresultsunveilnewcharacteristicsof twodistinctpermeabilizationmechanismsassociatedwithP2X7receptorsinmacrophagesandprovidethefirstevidence indicating that these pathways

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