2024
Enhancing in vivo cell and tissue targeting by modulation of polymer nanoparticles and macrophage decoys
Piotrowski-Daspit A, Bracaglia L, Eaton D, Richfield O, Binns T, Albert C, Gould J, Mortlock R, Egan M, Pober J, Saltzman W. Enhancing in vivo cell and tissue targeting by modulation of polymer nanoparticles and macrophage decoys. Nature Communications 2024, 15: 4247. PMID: 38762483, PMCID: PMC11102454, DOI: 10.1038/s41467-024-48442-7.Peer-Reviewed Original ResearchConceptsPoly(amine-co-esterPolymer nanoparticlesDelivery of nucleic acid therapeuticsCell-type tropismTissue tropismNucleic acid delivery vehiclesIn vivo deliveryIn vivo efficacyCirculation half-lifeNucleic acid therapeuticsVehicle characteristicsTunable propertiesBiodistribution assessmentPhysiological fatePolymer chemistrySurface propertiesPharmacokinetic modelTissue targetingNanoparticlesDistribution modifiersPolymeric nanoparticlesTropismPolymerDelivery vehiclesHalf-life
2022
Co-Expression and Functional Interactions of Death Receptor 3 and E-Selectin in Clear Cell Renal Cell Carcinoma
Al-Lamki RS, Wang J, Pober JS, Bradley JR. Co-Expression and Functional Interactions of Death Receptor 3 and E-Selectin in Clear Cell Renal Cell Carcinoma. American Journal Of Pathology 2022, 192: 722-736. PMID: 35063404, DOI: 10.1016/j.ajpath.2021.12.010.Peer-Reviewed Original ResearchConceptsMitogen-activated protein kinaseCell cycle entryCcRCC cellsDeath receptor 3Protein kinaseClear cell renal cell carcinoma cellsProximity ligation assayRenal cell carcinoma cellsReceptor 3E-selectinPotential new targetsCycle entryNF-κB-dependent mannerNF-κBLigation assayTumor gradeCcRCC tissuesFunctional interactionSelectin expressionFunctional roleClear cell renal cell carcinomaOrgan cultureCell renal cell carcinomaExpression increasesAddition of TL1A
2021
Coronavirus Disease 2019 (COVID-19) Coronary Vascular Thrombosis Correlation with Neutrophil but Not Endothelial Activation
Johnson JE, McGuone D, Xu ML, Jane-Wit D, Mitchell RN, Libby P, Pober JS. Coronavirus Disease 2019 (COVID-19) Coronary Vascular Thrombosis Correlation with Neutrophil but Not Endothelial Activation. American Journal Of Pathology 2021, 192: 112-120. PMID: 34599881, PMCID: PMC8479934, DOI: 10.1016/j.ajpath.2021.09.004.Peer-Reviewed Original ResearchConceptsVascular cell adhesion molecule-1Intracellular adhesion molecule-1Adhesion molecule-1Von Willebrand factorEndothelial activationMolecule-1Severe coronavirus disease 2019Neutrophil extracellular trap formationCell adhesion molecule-1COVID-19 cohortCOVID-19 patientsNeutrophil-platelet aggregatesCoronavirus disease 2019Extracellular trap formationCOVID-19Transcription factor p65Extensive thrombosisLymphocytic infiltrationMyocardial injuryThrombotic diathesisInflammatory activationNeutrophil activationCardiovascular diseaseDisease 2019Autopsy tissueDifferential inflammatory responses of the native left and right ventricle associated with donor heart preservation
Lei I, Huang W, Ward PA, Pober JS, Tellides G, Ailawadi G, Pagani FD, Landstrom AP, Wang Z, Mortensen RM, Cascalho M, Platt J, Chen Y, Lam HYK, Tang PC. Differential inflammatory responses of the native left and right ventricle associated with donor heart preservation. Physiological Reports 2021, 9: e15004. PMID: 34435466, PMCID: PMC8387788, DOI: 10.14814/phy2.15004.Peer-Reviewed Original ResearchConceptsRight ventricleCold ischemiaIL-10Inflammatory responseIL-6 protein levelsCold ischemic preservationEx vivo ischemiaLeft ventricle dysfunctionCold ischemic timeDonor heart preservationInflammatory cytokine expressionCell deathDifferential inflammatory responseTumor necrosis factorComparable inflammatory responsesHuman donor heartsCaspase-3 expressionIschemic preservationVentricle dysfunctionInflammasome expressionIschemic timeRNA sequencingContractile dysfunctionDonor heartsWarm perfusion
2020
Mural Cell-Specific Deletion of Cerebral Cavernous Malformation 3 in the Brain Induces Cerebral Cavernous Malformations
Wang K, Zhang H, He Y, Jiang Q, Tanaka Y, Park IH, Pober JS, Min W, Zhou HJ. Mural Cell-Specific Deletion of Cerebral Cavernous Malformation 3 in the Brain Induces Cerebral Cavernous Malformations. Arteriosclerosis Thrombosis And Vascular Biology 2020, 40: 2171-2186. PMID: 32640906, DOI: 10.1161/atvbaha.120.314586.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosis Regulatory ProteinsBrainCell CommunicationCell MovementCells, CulturedCoculture TechniquesEndothelial CellsFemaleFocal AdhesionsGene DeletionGenetic Predisposition to DiseaseHemangioma, Cavernous, Central Nervous SystemHumansMaleMembrane ProteinsMice, KnockoutMicrovesselsMyocytes, Smooth MusclePaxillinPericytesPhenotypeProtein StabilityProto-Oncogene ProteinsSignal TransductionConceptsCerebral cavernous malformationsBrain mural cellsCCM lesionsMural cellsCavernous malformationsSevere brain hemorrhageCCM pathogenesisSmooth muscle cellsWeeks of ageCell-specific deletionMural cell coverageBrain pericytesBrain hemorrhageNeonatal stageBrain vasculatureLesionsEntire brainMuscle cellsCerebral cavernous malformation 3Endothelial cellsMicePericytesSpecific deletionAdhesion formationPathogenesisComplement activated interferon-γ-primed human endothelium transpresents interleukin-15 to CD8+ T cells
Xie CB, Jiang B, Qin L, Tellides G, Kirkiles-Smith NC, Jane-wit D, Pober JS. Complement activated interferon-γ-primed human endothelium transpresents interleukin-15 to CD8+ T cells. Journal Of Clinical Investigation 2020, 130: 3437-3452. PMID: 32191642, PMCID: PMC7324183, DOI: 10.1172/jci135060.Peer-Reviewed Original ResearchConceptsIL-15/IL-15Rα complexesIL-1βHuman endothelial cellsMembrane attack complexEndothelial cellsAcute rejectionT cellsT cell-mediated acute rejectionCell-mediated acute rejectionComplement-mediated pathologiesIL-15Rα expressionGraft endothelial cellsHuman coronary artery graftsEffector memory CD4T cell infiltrationCoronary artery graftsIL-1 receptorActive IL-1βCultured human endothelial cellsNLRP3 inflammasome assemblyNoncanonical NF-κBArtery graftAlloreactive CD8Complement membrane attack complexMemory CD4
2019
Endothelial Cell–Derived Interleukin-18 Released During Ischemia Reperfusion Injury Selectively Expands T Peripheral Helper Cells to Promote Alloantibody Production
Liu L, Fang C, Fu W, Jiang B, Li G, Qin L, Rosenbluth J, Gong G, Xie CB, Yoo P, Tellides G, Pober JS, Jane-Wit D. Endothelial Cell–Derived Interleukin-18 Released During Ischemia Reperfusion Injury Selectively Expands T Peripheral Helper Cells to Promote Alloantibody Production. Circulation 2019, 141: 464-478. PMID: 31744330, PMCID: PMC7035199, DOI: 10.1161/circulationaha.119.042501.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDelayed Graft FunctionFemaleGene Expression RegulationHuman Umbilical Vein Endothelial CellsHumansImmunoglobulin MInflammasomesInterleukin-18Interleukin-18 Receptor alpha SubunitIsoantibodiesMiceMice, SCIDOrgan TransplantationReperfusion InjurySignal TransductionT-Lymphocytes, Helper-InducerConceptsIschemia-reperfusion injuryDonor-specific antibodiesPeripheral helper cellsIL-18Helper cellsReperfusion injuryInterleukin-18IL-18R1Donor-specific antibody formationEndothelial cellsDelayed graft functionLate allograft lossT cell populationsAlloantibody productionAllograft lossChronic rejectionGraft functionClinical manifestationsPD-L2Antibody formationHumanized modelAllograft tissueImmunoglobulin MPatient specimensComplement activation
2016
Eculizumab Therapy for Chronic Antibody‐Mediated Injury in Kidney Transplant Recipients: A Pilot Randomized Controlled Trial
Kulkarni S, Kirkiles‐Smith N, Deng YH, Formica RN, Moeckel G, Broecker V, Bow L, Tomlin R, Pober JS. Eculizumab Therapy for Chronic Antibody‐Mediated Injury in Kidney Transplant Recipients: A Pilot Randomized Controlled Trial. American Journal Of Transplantation 2016, 17: 682-691. PMID: 27501352, DOI: 10.1111/ajt.14001.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAntibodies, Monoclonal, HumanizedChronic DiseaseComplement C5Complement Inactivating AgentsEarly Intervention, EducationalFemaleFollow-Up StudiesGlomerular Filtration RateGraft RejectionGraft SurvivalHumansIsoantibodiesKidney Failure, ChronicKidney Function TestsKidney TransplantationLiving DonorsMaleMiddle AgedPilot ProjectsPrognosisRisk FactorsTissue DonorsTransplant RecipientsYoung AdultConceptsDe novo donor-specific antibodiesComplement inhibitionTreatment groupsNovo donor-specific antibodiesAntibody-Mediated InjuryC1q-positive patientsDonor-specific antibodiesKidney transplant recipientsPrimary end pointEndothelial cell injuryMo of observationEculizumab therapyEculizumab treatmentHumoral injuryTransplant recipientsKidney transplantRenal functionKidney functionChronic settingEGFR trajectoriesTreatment periodCell injuryPatientsEnd pointPercentage change
2015
Tissue-Engineered Microvasculature to Reperfuse Isolated Renal Glomeruli
Chang WG, Fornoni A, Tietjen G, Mendez JJ, Niklason LE, Saltzman WM, Pober JS. Tissue-Engineered Microvasculature to Reperfuse Isolated Renal Glomeruli. Tissue Engineering Part A 2015, 21: 2673-2679. PMID: 26414101, PMCID: PMC4652181, DOI: 10.1089/ten.tea.2015.0060.Peer-Reviewed Original ResearchEfficient Gene Disruption in Cultured Primary Human Endothelial Cells by CRISPR/Cas9
Abrahimi P, Chang WG, Kluger MS, Qyang Y, Tellides G, Saltzman WM, Pober JS. Efficient Gene Disruption in Cultured Primary Human Endothelial Cells by CRISPR/Cas9. Circulation Research 2015, 117: 121-128. PMID: 25940550, PMCID: PMC4490936, DOI: 10.1161/circresaha.117.306290.Peer-Reviewed Original ResearchAnimalsCD4-Positive T-LymphocytesCell SeparationCells, CulturedCRISPR-Cas SystemsEndothelial Progenitor CellsFemaleFetal BloodGene DeletionGene Knockout TechniquesGenes, MHC Class IIGenetic VectorsHLA-DR AntigensHumansIntracellular Signaling Peptides and ProteinsLentivirusLymphocyte ActivationLymphocyte Culture Test, MixedMiceMice, SCIDNuclear ProteinsPrimary Cell CultureProteinsTetracyclineTrans-ActivatorsVesicular Transport Proteins
2013
Sustained delivery of proangiogenic microRNA‐132 by nanoparticle transfection improves endothelial cell transplantation
Devalliere J, Chang WG, Andrejecsk JW, Abrahimi P, Cheng CJ, Jane‐wit D, Saltzman WM, Pober JS. Sustained delivery of proangiogenic microRNA‐132 by nanoparticle transfection improves endothelial cell transplantation. The FASEB Journal 2013, 28: 908-922. PMID: 24221087, PMCID: PMC3898640, DOI: 10.1096/fj.13-238527.Peer-Reviewed Original ResearchConceptsHuman umbilical vein ECsEndothelial cellsMiR-132MicroRNA-132Cultured human umbilical vein endothelial cellsNumber of microvesselsGrowth factor-induced proliferationHuman umbilical vein endothelial cellsUmbilical vein endothelial cellsEndothelial cell transplantationCultured endothelial cellsEndogenous growth factorsEC transplantationVein endothelial cellsCell transplantationImmunodeficient miceTissue perfusionTransplantationMiR deliveryGrowth factorIntegrin αvβ3Endocytosed nanoparticlesSquare millimeterBiological effectsControl transfectionAlloantibody and Complement Promote T Cell–Mediated Cardiac Allograft Vasculopathy Through Noncanonical Nuclear Factor-&kgr;B Signaling in Endothelial Cells
Jane-wit D, Manes TD, Yi T, Qin L, Clark P, Kirkiles-Smith NC, Abrahimi P, Devalliere J, Moeckel G, Kulkarni S, Tellides G, Pober JS. Alloantibody and Complement Promote T Cell–Mediated Cardiac Allograft Vasculopathy Through Noncanonical Nuclear Factor-&kgr;B Signaling in Endothelial Cells. Circulation 2013, 128: 2504-2516. PMID: 24045046, PMCID: PMC3885874, DOI: 10.1161/circulationaha.113.002972.Peer-Reviewed Original ResearchConceptsCardiac allograft vasculopathyPanel reactive antibodyNuclear factor-κB signalingFactor-κB signalingAllograft vasculopathyT cellsEndothelial cellsMembrane attack complexAlloreactive T cell activationChronic antibody-mediated rejectionNoncanonical nuclear factorProinflammatory gene programAntibody-mediated rejectionDonor-specific antibodiesGraft endothelial cellsLate allograft lossAlloreactive T cellsAllogeneic endothelial cellsT cell activationAttack complexHuman T cellsAllograft lossHeart transplantationTransplantation patientsLesion pathogenesis
1998
Endothelial cells in physiology and in the pathophysiology of vascular disorders.
Cines DB, Pollak ES, Buck CA, Loscalzo J, Zimmerman GA, McEver RP, Pober JS, Wick TM, Konkle BA, Schwartz BS, Barnathan ES, McCrae KR, Hug BA, Schmidt AM, Stern DM. Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood 1998, 91: 3527-61. PMID: 9572988.Peer-Reviewed Original ResearchAnimalsArteriosclerosisBlood CellsBlood CoagulationCell AdhesionCell Adhesion MoleculesCell DifferentiationCells, CulturedEndothelial Growth FactorsEndothelinsEndothelium, VascularEpoprostenolExtracellular MatrixFemaleFibrinolysisFibroblast Growth Factor 2HemodynamicsHumansInflammationLymphokinesMaleMiceNeovascularization, PhysiologicNitric OxidePlatelet Activating FactorPre-EclampsiaPregnancyThrombosisUmbilical VeinsVascular DiseasesVascular Endothelial Growth Factor AVascular Endothelial Growth Factors
1997
Pig but not human interferon-γ initiates human cell-mediated rejection of pig tissue in vivo
Sultan P, Murray A, McNiff J, Lorber M, Askenase P, Bothwell A, Pober J. Pig but not human interferon-γ initiates human cell-mediated rejection of pig tissue in vivo. Proceedings Of The National Academy Of Sciences Of The United States Of America 1997, 94: 8767-8772. PMID: 9238052, PMCID: PMC23121, DOI: 10.1073/pnas.94.16.8767.Peer-Reviewed Original ResearchConceptsHuman peripheral blood mononuclear cellsPeripheral blood mononuclear cellsPig skin graftsCell-mediated rejectionBlood mononuclear cellsIFN-gammaMononuclear cellsSkin graftsDermal microvesselsMajor histocompatibility complex (MHC) molecule expressionT cell-mediated rejectionPerivascular mononuclear cell infiltratesClass II major histocompatibility complex moleculesMononuclear cell infiltrateMajor histocompatibility complex moleculesTumor necrosis factorEvidence of injuryHistocompatibility complex moleculesPig endothelial cellsCell infiltrateIntradermal injectionMolecule expressionSparse infiltrateIntraperitoneal inoculationMouse microvessels
1991
Recruitment of neutrophils in the local endotoxin response: association with de novo endothelial expression of endothelial leukocyte adhesion molecule-1.
Munro JM, Pober JS, Cotran RS. Recruitment of neutrophils in the local endotoxin response: association with de novo endothelial expression of endothelial leukocyte adhesion molecule-1. Laboratory Investigation 1991, 64: 295-9. PMID: 1705305.Peer-Reviewed Original ResearchConceptsELAM-1 expressionEndothelial expressionAdhesion moleculesEndotoxin responseICAM-1ELAM-1Endothelial adhesion molecule expressionEndothelial leukocyte adhesion molecule-1Mononuclear cell extravasationLeukocyte adhesion molecule-1Mononuclear cell accumulationRecruitment of neutrophilsEndothelial leukocyte adhesion moleculeInjection of endotoxinICAM-1 expressionAdhesion molecule expressionPolymorphonuclear leucocyte accumulationAdhesion molecule-1Intercellular adhesion moleculeLeukocyte adhesion moleculesExtravasation of PMNsPMN accumulationEosin-stained paraffin sectionsFactor injectionsPMN infiltration
1989
ENDOTHELIAL CELL ACTIVATION AND HIGH INTERLEUKIN-1 SECRETION IN THE PATHOGENESIS OF ACUTE KAWASAKI DISEASE
Leung D, Kurt-Jones E, Newburger J, Cotran R, Burns J, Pober J. ENDOTHELIAL CELL ACTIVATION AND HIGH INTERLEUKIN-1 SECRETION IN THE PATHOGENESIS OF ACUTE KAWASAKI DISEASE. The Lancet 1989, 334: 1298-1302. PMID: 2480498, DOI: 10.1016/s0140-6736(89)91910-7.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, SurfaceCell AdhesionCell Adhesion MoleculesChild, PreschoolEndothelium, VascularE-SelectinFemaleGamma-GlobulinsHLA-DQ AntigensHumansImmunization, PassiveIntercellular Adhesion Molecule-1Interleukin-1MaleMembrane GlycoproteinsMucocutaneous Lymph Node SyndromeReceptors, ImmunologicSkinConceptsEndothelial cell activationCoronary artery abnormalitiesCell activationInterleukin-1Gammaglobulin treatmentArtery abnormalitiesKawasaki diseaseAcute Kawasaki disease patientsPeripheral blood mononuclear cellsEndothelial cellsCytotoxic antibody activityIntravenous gammaglobulin treatmentKawasaki disease patientsAcute Kawasaki diseaseEndothelial cell antigensBlood mononuclear cellsInterleukin-1 secretionTumor necrosis factorIL-1 secretionEndothelial cell expressionSkin biopsy samplesMeans of immunoperoxidaseMucocutaneous symptomsPersistent feverClinical symptomsTumor necrosis factor and interferon-gamma induce distinct patterns of endothelial activation and associated leukocyte accumulation in skin of Papio anubis.
Munro JM, Pober JS, Cotran RS. Tumor necrosis factor and interferon-gamma induce distinct patterns of endothelial activation and associated leukocyte accumulation in skin of Papio anubis. American Journal Of Pathology 1989, 135: 121-33. PMID: 2505619, PMCID: PMC1880213.Peer-Reviewed Original ResearchConceptsLeukocyte accumulationNecrosis factorIFN-gammaEndothelial cell antigen expressionAdhesion moleculesAnti-intercellular adhesion moleculeEndothelial cell hypertrophyPolymorphonuclear leukocyte accumulationTumor necrosis factorCytokine-activated endotheliumLeukocyte adhesion moleculesCell antigen expressionImmune inflammationEndothelial activationLeukocyte infiltrationHypersensitivity reactionsMononuclear cellsHLA-DPEnvelope antigenAntigen expressionVascular permeabilitySubsequent extravasationRecombinant human interferonCell hypertrophyEndothelial morphology
1988
LYTIC ANTI-ENDOTHELIAL CELL ANTIBODIES IN HAEMOLYTIC-URAEMIC SYNDROME
Leung D, Havens P, Moake J, Kim M, Pober J. LYTIC ANTI-ENDOTHELIAL CELL ANTIBODIES IN HAEMOLYTIC-URAEMIC SYNDROME. The Lancet 1988, 332: 183-186. PMID: 2899661, DOI: 10.1016/s0140-6736(88)92287-8.Peer-Reviewed Original ResearchConceptsAnti-endothelial cell antibodiesHaemolytic uraemic syndromeThrombotic thrombocytopenic purpuraCell antibodiesComplement-fixing IgGDisorder of immunoregulationAnti-endothelial antibodiesEndothelial cell antigensCultured human umbilical vein endothelial cellsGamma-interferon treatmentHuman umbilical vein endothelial cellsUmbilical vein endothelial cellsAdult patientsVein endothelial cellsThrombocytopenic purpuraIgM antibodiesVascular injuryInterferon treatmentUraemic syndromeGamma interferonCell antigensControl seraEndothelial cellsAntibodiesSerum
1987
Composition of the von Willebrand factor storage organelle (Weibel-Palade body) isolated from cultured human umbilical vein endothelial cells.
Ewenstein BM, Warhol MJ, Handin RI, Pober JS. Composition of the von Willebrand factor storage organelle (Weibel-Palade body) isolated from cultured human umbilical vein endothelial cells. Journal Of Cell Biology 1987, 104: 1423-1433. PMID: 3494734, PMCID: PMC2114468, DOI: 10.1083/jcb.104.5.1423.Peer-Reviewed Original ResearchConceptsWeibel-Palade bodiesSecretory organellesUmbilical vein endothelial cellsOrganelle fractionsVein endothelial cellsCultured endothelial cellsIntracellular protein traffickingVon Willebrand factorVon Willebrand factor storageEndothelial cellsSelf-generating Percoll gradientsDirect morphological examinationCultured umbilical vein endothelial cellsUnmodified formProtein traffickingCultured human umbilical vein endothelial cellsRegulated secretionStimulation of ECHuman umbilical vein endothelial cellsStorage organellesOrganellesDense organellesPro sequenceProteolytic processingAdhesive glycoprotein
1986
Two monokines, interleukin 1 and tumor necrosis factor, render cultured vascular endothelial cells susceptible to lysis by antibodies circulating during Kawasaki syndrome.
Leung DY, Geha RS, Newburger JW, Burns JC, Fiers W, Lapierre LA, Pober JS. Two monokines, interleukin 1 and tumor necrosis factor, render cultured vascular endothelial cells susceptible to lysis by antibodies circulating during Kawasaki syndrome. Journal Of Experimental Medicine 1986, 164: 1958-1972. PMID: 3491174, PMCID: PMC2188474, DOI: 10.1084/jem.164.6.1958.Peer-Reviewed Original ResearchConceptsAcute Kawasaki syndromeTumor necrosis factorKawasaki syndromeHuman endothelial cellsIL-1Cytotoxic antibodiesImmune activationEndothelial cellsNecrosis factorTarget antigenComplement-dependent cytotoxic activityAcute febrile illnessEndothelial cell antigensVascular smooth muscle cellsAge-matched controlsMonocytes/macrophagesSmooth muscle cellsCultured vascular endothelial cellsVascular endothelial cellsComplement-mediated killingDiffuse vasculitisConvalescent phaseFebrile illnessAcute phaseVascular injury