简介:ObjectivesToinvestigatetheassociationofsolubleFasligand(sFasL)andsolubleFasreceptor(sFas)withhumanchroniccongestiveheartfailure(CHF).MethodsTheserumlevelofsFasLandsFasin33patientswithCHF(13incardiacfunctionclassⅡ,17inclassⅢ,3inclassⅣ,NYHA)wasassessedwithenzyme-linkedimmunosorbentassay,andwascomparedwiththatof18age-,bloodpressure-matchedpatientswithcardiacfunctionclassⅠ(NYHA).ResultsTherewasnodifferenceinthelevelofsFasLbetweenthetwogroups[CHFgroup:231.50+/-84.50(cardiacfunctionclassⅡ216.50+/-96.00,classⅢ226.80+/-85.70,classⅣ244.00+/-73.00)vs.cardiacfunctionclassIgroup:217.50+/-89.00pg/mL,P>0.05].However,thelevelofsFaswassignificantlyhigherinthepatientswithCHFthanthoseofcardiacfunctionclassIgroup[CHFgroup:1353.30+/-507.71(cardiacfunctionclassⅡ1154.85+/-371.20,classⅢ1412.88+/-493.62,classⅣ1875.67+/-806.
简介:<正>Fasligand(FasL)wasfirstdescribedfunctionallyasaninduciblecellsurfacemoleculeusedbycytotoxicTcellstoinduceapoptoticcelldeathintumorcellsandactivatedlymphocytes.WiththeidentificationofFasastheIprgeneproduct,FasLbecamerecognizedasamoleculeinvolvedindown-regulationoftheimmunesystem.WhileFasLcanbeusedtoefficientlykillFas-expressingtumorcellsaswellasactivatedTandBlymphocytesinvitro,attemptstouseFasLtherapeuticallytotreatcancerortopreventtransplant
简介:ApoptosisproducedinBcellsthroughFas(APO-1,CD95)triggeringisregulatedbysignalsderivedfromothersurfacereceptors:CD40engagementproducesupregulationofFasexpressionandmarkedsusceptibilitytoFas-inducedcelldeath,whereasantigenreceptorengagement,orIL-4Rengagement,inhibitsFaskillingandinsodoinginducesastateofFas-resistance,eveninotherwisesensitive,CD40-stimulatedtargets.SurfaceimmunoglobulinandIL-4RutilizeatleastpartiallydistinctpathwaystoproduceFas-resistancethatdifferentiallydependonPKCandSTAT6,respectively.Further,surfaceimmunoglobulinsignalingforinducibleFas-resistancebypassesBtk,requiresNF-κB,andentailsnewmacromolecularsynthesis.TerminaleffectorsofBcellFas-resistanceincludetheknownanti-apoptoticgeneproducts,Bcl-XLandFLIP,andanovelanti-apoptoticgenethatencodesFAIM(FasApoptosisInhibitoryMolecule).faimwasidentifiedbydifferentialdisplayandexistsintwoalternativelysplicedforms;faim-Sisbroadlyexpressed,butfaim-Lexpressionistissue-specific.TheFAIMsequenceishighlyevolutionarilyconserved,suggestinganimportantroleforthismoleculethroughoutphylogeny.InducibleresistancetoFaskillingishypothesizedtoprotectforeignantigen-specificBcellsduringpotentiallyhazardousinteractionswithFasL-bearingTcells,whereasautoreactiveBcellsfailtobecomeFas-resistantandaredeletedviaFas-dependentcytotoxicity.InadvertentoraberrantacquisitionofFas-resistancemaypermitautoreactiveBcellstoescapeFasdeletion,andmalignantlymphocytestoimpedeanti-tumorimmunity.
简介:<正>ThesusceptibilityofprimaryBcellstoFas(APO-1,CD95)-mediatedapoptosisisregulatedbysignalsderivedfromadditionalsurfacereceptors.CD40engagementproducesupregulationofFasexpressionandinducesmarkedsensitivitytoFas-inducedcelldeath,whereasBcellantigenreceptor(BCR)engagementinhibitsFaskillingandtherebyproducesFas-resistance,eveninotherwisesusceptible,CD40-stimulatedtargets.BCRsignalingforinducibleFas-resistancedevelopsoveraperiodof12hoursanddependson
简介:IncreasedexpressionofFasbyhematopoieticprogenitorsinaplasticanemia(AA)suggeststhatFas/Fasligand(FasL)systemplaysakeyroleintheformationofseverepancytopenia.Tofurtherconfirmtheabovehypothesis,Tcellsfrom8patientswithAAweresystematicallystudiedfortheirFasL'sdistributionpattern,releasingmannerandproapoptoticactivity,comparedwithnormalrestingTcellsandartificiallyactivatedTcellblasts.TheresultsdemonstratedthatAATcellsabnormallyexpressedlowlevelsofmembrane-boundFasLandcontainedhighlevelsofintracellularFasLwhichcouldbetriggeredtoreleasebyhigh-dosephytohemagglutinin(PHA)pulse-stimulation.ThesupernatantsfromthePHA-stimulatedAATcellshadapparentcytotoxicityagainstFasL-sensitiveJurkatcells,whichcouldbesignificantlyinhibitedbymonoclonalantibodyagainstFasLinadose-dependentmanner,ornearlycompletelyabrogatedbyultracentrifugation.TheabovephenomenaalsoappearedonartificiallyactivatedTcellblasts,butthiswasnotthecaseonnormalrestingTcells.TheseresultsindicatethatAATcellisatypeof'preactivated'Tlymphocyte,characterizedbyoverexpressionofFasL,especiallyintracellularFasLwhichcanbestimulatedtoreleaseinbioavtiveexosomesboundform.Takentogether,ourdataprovidefurtheranddirectevidenceforthehypothesisthatTcellsmightmediatethedestructionofhematopieticprogenitorinAAthroughFas/FasLsystem.