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首页> 外文期刊>Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society >Human neutrophil formyl peptide receptor phosphorylation and the mucosal inflammatory response
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Human neutrophil formyl peptide receptor phosphorylation and the mucosal inflammatory response

机译:人中性粒细胞甲酰基肽受体磷酸化与黏膜炎症反应

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Bacterial/mitochondrialfMLFanalogsbindFPR1,drivingaccumulation/activationofPMNatsitesofinfection/injury,whilepromotingwoundhealinginepithelia.WequantifiedlevelsofUFPR1andTFPR1inisolatedPMNbyuseofphosphosensitiveNFPRbandphosphorylation‐independentNFPRaantibodies.UFPR1andtotalTFPRwereassessedinflamedmucosa,observedinhumanIBD.InisolatedPMNafterfMLFstimulation,UFPR1declined70%(fMLFEC50=11±1nM;t1/2=15s)andwasstableforupto4h,whereasTFPR1changedonlyslightly.Antagonists(tBoc‐FLFLF,CsH)andmetabolicinhibitorNaFpreventedthefMLF‐dependentUFPR1decrease.AnnexinA1fragmentAc2‐26alsoinduceddecreasesinUFPR1(Ac2‐26EC50~3μM).Proinflammatoryagents(TNF‐α,LPS),phosphataseinhibitor(okadaicacid),andG‐proteinactivator(MST)modestlyincreasedfMLFEC50,2‐to4‐fold,whereasPTX,Ca2+chelators(EGTA/BAPTA),H2O2,GM‐CSF,ENA‐78,IL‐1RA,andLXA4hadnoeffect.Aggregation‐inducingPAF,however,stronglyinhibitedfMLF‐stimulatedUFPR1decreases.fMLF‐drivenPMNalsodemonstrateddecreasedUFPR1aftertraversingmonolayersofculturedintestinalepithelialcells,asdidPMNinintestinalmucosalsamples,demonstratingactiveinflammationfromUCpatients.TotalTFPRremainedhighinPMNwithininflamedcrypts,migratingthroughcryptepithelium,andinthelaminapropria‐adjoiningcrypts,butUFPR1wasonlyobservedatsomeperipheralsitesoncryptaggregates.LossofUFPR1inPMNresultsfromC‐terminalS/Tphosphorylation.OurresultssuggestGprotein–insensitive,fMLF‐dependentFPR1phosphorylationinisolatedsuspensionPMN,whichmaymanifestinfMLF‐driventransmigrationandpotentially,inactivelyinflamedtissues,exceptatminordiscretesurfacelocationsofPMN‐containingcryptaggregates...
机译:细菌/ mitochondrialfMLFanalogsbindFPR1,drivingaccumulation / activationofPMNatsitesofinfection /损伤,whilepromotingwoundhealinginepithelia.WequantifiedlevelsofUFPR1andTFPR1inisolatedPMNbyuseofphosphosensitiveNFPRbandphosphorylation-independentNFPRaantibodies.UFPR1andtotalTFPRwereassessedinflamedmucosa,observedinhumanIBD.InisolatedPMNafterfMLFstimulation,UFPR1declined70%(fMLFEC50 = 11±1nm的; T1 / 2 = 15秒)andwasstableforupto4h,whereasTFPR1changedonlyslightly.Antagonists(TBOC-FLFLF,CSH)andmetabolicinhibitorNaFpreventedthefMLF依赖的UFPR1降低.AnnexinA1片段Ac2‐26也引起UFPR1(Ac2‐26EC50〜3μM)的降低。促炎药(TNF‐α,LPS),磷酸酶抑制剂(冈田酸)和G蛋白活化剂(MST)适度增加了fMLFEC50,Ca2 + 2 = 4 BAPTA),H2O2,GM‐CSF,ENA‐78,IL‐1RA和LXA4没有影响。聚集诱导的PAF强烈抑制了fMLF刺激的UFPR1降低.fMLF驱动的PMN也表明在经过单层培养后的粪便测试后,凹坑中的UFPR1降低了ialcells,asdidPMNinintestinalmucosalsamples,demonstratingactiveinflammationfromUCpatients.TotalTFPRremainedhighinPMNwithininflamedcrypts,migratingthroughcryptepithelium,andinthelaminapropria-adjoiningcrypts,butUFPR1wasonlyobservedatsomeperipheralsitesoncryptaggregates.LossofUFPR1inPMNresultsfromC的终端/ Tphosphorylation.OurresultssuggestGprotein不敏感,fMLF-dependentFPR1phosphorylationinisolatedsuspensionPMN,whichmaymanifestinfMLF-driventransmigrationandpotentially,inactivelyinflamedtissues,exceptatminordiscretesurfacelocationsofPMN-containingcryptaggregates ...

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