Mechanisms for Vascular Cell Adhesion Molecule-1 Activation of ERK12 during Leukocyte Transendothelial Migration 英文参考文献.docVIP

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Mechanisms for Vascular Cell Adhesion Molecule-1 Activation of ERK12 during Leukocyte Transendothelial Migration 英文参考文献.doc

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Mechanisms for Vascular Cell Adhesion Molecule-1 Activation of ERK12 during Leukocyte Transendothelial Migration 英文参考文献

MechanismsforVascularCellAdhesionMolecule-1 ActivationofERK1/2duringLeukocyteTransendothelial Migration HiamAbdala-Valencia,SergejsBerdnikovs,JoanM.Cook-Mills* Allergy-ImmunologyDivision,NorthwesternUniversityFeinbergSchoolofMedicine,Chicago,Illinois,UnitedStatesofAmerica Abstract Background:Duringinflammation,adhesionmoleculesregulaterecruitmentofleukocytestoinflamedtissues.Itisreported that vascular cell adhesion molecule-1 (VCAM-1) activates extracellular regulated kinases 1 and 2 (ERK1/2), but the mechanismforthisactivationisnotknown.PharmacologicalinhibitorsofERK1/2partiallyinhibitleukocytetransendothelial migrationinamulti-receptorsystembutitisnotknownwhetherVCAM-1activationofERK1/2is requiredforleukocyte transendothelialmigration(TEM)onVCAM-1. Methodology/PrincipalFindings:Inthisstudy,weidentifiedamechanismforVCAM-1activationofERK1/2inhumanand mouseendothelialcells.VCAM-1signaling,whichoccursthroughendothelialcellNADPHoxidase,proteinkinaseCa(PKCa), andproteintyrosinephosphatase1B(PTP1B),activatesendothelialcellERK1/2.InhibitionofthesesignalsblockedVCAM-1 activation of ERK1/2, indicating that ERK1/2 is activated downstream of PTP1B during VCAM-1 signaling. Furthermore, VCAM-1-specific leukocyte migration under physiological laminar flow of 2 dynes/cm2 was blocked by pretreatment of endothelialcellswithdominant-negativeERK2K52RortheMEK/ERKinhibitors,PD98059andU0126,indicatingforthefirst timethatERKregulatesVCAM-1-dependentleukocytetransendothelialmigration. Conclusions/Significance: VCAM-1 activation of endothelial cell NADPH oxidase/PKCa/PTP1B induces transient ERK1/2 activationthatisnecessaryforVCAM-1-dependentleukocyteTEM. Citation: Abdala-Valencia H, Berdnikovs S, Cook-Mills JM (2011) Mechanisms for Vascular Cell Adhesion Molecule-1 Activation of ERK1/2 during Leukocyte TransendothelialMigration.PLoSONE6(10):e26706.doi:10.1371/journal.pone.0026706 Editor:Wing-KinSyn,InstituteofHepatologyLondon,UnitedKingdom ReceivedJuly27,2011;AcceptedOctober2,201