2024
Ezrin drives adaptation of monocytes to the inflamed lung microenvironment
Gudneppanavar R, Di Pietro C, H Öz H, Zhang P, Cheng E, Huang P, Tebaldi T, Biancon G, Halene S, Hoppe A, Kim C, Gonzalez A, Krause D, Egan M, Gupta N, Murray T, Bruscia E. Ezrin drives adaptation of monocytes to the inflamed lung microenvironment. Cell Death & Disease 2024, 15: 864. PMID: 39613751, PMCID: PMC11607083, DOI: 10.1038/s41419-024-07255-8.Peer-Reviewed Original ResearchConceptsActivation of focal adhesion kinaseExtracellular matrixActin-binding proteinsFocal adhesion kinaseLung extracellular matrixKnock-out mouse modelProtein kinase signalingCortical cytoskeletonLoss of ezrinKinase signalingPlasma membraneCell migrationSignaling pathwayEzrinResponse to lipopolysaccharideTissue-resident macrophagesMouse modelLipopolysaccharideCytoskeletonEzrin expressionLung microenvironmentKinaseMonocyte recruitmentProteinAkt
2022
Recruited monocytes/macrophages drive pulmonary neutrophilic inflammation and irreversible lung tissue remodeling in cystic fibrosis
Öz H, Cheng E, Di Pietro C, Tebaldi T, Biancon G, Zeiss C, Zhang P, Huang P, Esquibies S, Britto C, Schupp J, Murray T, Halene S, Krause D, Egan M, Bruscia E. Recruited monocytes/macrophages drive pulmonary neutrophilic inflammation and irreversible lung tissue remodeling in cystic fibrosis. Cell Reports 2022, 41: 111797. PMID: 36516754, PMCID: PMC9833830, DOI: 10.1016/j.celrep.2022.111797.Peer-Reviewed Original ResearchConceptsC motif chemokine receptor 2Monocytes/macrophagesLung tissue damageCystic fibrosisTissue damageCF lungPulmonary neutrophilic inflammationPro-inflammatory environmentChemokine receptor 2CF lung diseaseNumber of monocytesSpecific therapeutic agentsGrowth factor βCF transmembrane conductance regulatorLung hyperinflammationLung neutrophiliaNeutrophilic inflammationNeutrophil inflammationInflammation contributesLung damageNeutrophil recruitmentLung diseaseLung tissueReceptor 2Therapeutic targetRecruitment of monocytes primed to express heme oxygenase-1 ameliorates pathological lung inflammation in cystic fibrosis
Di Pietro C, Öz HH, Zhang PX, Cheng EC, Martis V, Bonfield TL, Kelley TJ, Jubin R, Abuchowski A, Krause DS, Egan ME, Murray TS, Bruscia EM. Recruitment of monocytes primed to express heme oxygenase-1 ameliorates pathological lung inflammation in cystic fibrosis. Experimental & Molecular Medicine 2022, 54: 639-652. PMID: 35581352, PMCID: PMC9166813, DOI: 10.1038/s12276-022-00770-8.Peer-Reviewed Original ResearchConceptsHeme oxygenase-1Cystic fibrosisOxygenase-1Myeloid differentiation factor 88Neutrophilic pulmonary inflammationChronic airway infectionDifferentiation factor 88HO-1 levelsDisease mouse modelPseudomonas aeruginosaRecruitment of monocytesResolution of inflammationMonocytes/macrophagesTreatment of CFConditional knockout miceMechanism of actionLung neutrophiliaNeutrophilic inflammationLung inflammationAirway infectionPulmonary diseasePulmonary inflammationFactor 88Lung damageProinflammatory cytokines
2016
Increased susceptibility of Cftr−/− mice to LPS-induced lung remodeling
Bruscia E, Zhang P, Barone C, Scholte BJ, Homer R, Krause D, Egan ME. Increased susceptibility of Cftr−/− mice to LPS-induced lung remodeling. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2016, 310: l711-l719. PMID: 26851259, PMCID: PMC4836110, DOI: 10.1152/ajplung.00284.2015.Peer-Reviewed Original ResearchConceptsLung pathologyCF miceImmune responseWT miceChronic inflammationCystic fibrosisAbnormal immune responseChronic pulmonary infectionPersistent immune responseWild-type littermatesCF mouse modelsPseudomonas aeruginosa lipopolysaccharideCF lung pathologyPulmonary infectionChronic administrationLPS exposurePersistent inflammationLung remodelingWT littermatesLung tissueOverall pathologyMouse modelInflammationChronic exposureBacterial products
2015
Pharmacological modulation of the AKT/microRNA-199a-5p/CAV1 pathway ameliorates cystic fibrosis lung hyper-inflammation
Zhang PX, Cheng J, Zou S, D'Souza AD, Koff JL, Lu J, Lee PJ, Krause DS, Egan ME, Bruscia EM. Pharmacological modulation of the AKT/microRNA-199a-5p/CAV1 pathway ameliorates cystic fibrosis lung hyper-inflammation. Nature Communications 2015, 6: 6221. PMID: 25665524, PMCID: PMC4324503, DOI: 10.1038/ncomms7221.Peer-Reviewed Original ResearchConceptsCF macrophagesMiR-199aMicroRNA-199aHyper-inflammatory responseCFTR-deficient miceCystic fibrosis patientsCystic fibrosis lungLung destructionDisease morbidityPharmacological modulationCF miceCF lungFibrosis patientsInnate immunityLungMacrophagesCAV1 expressionDrug celecoxibReduced levelsTLR4CelecoxibMiceCav1PathwayMorbidity
2013
Very Small Embryonic‐Like Stem Cells from the Murine Bone Marrow Differentiate into Epithelial Cells of the Lung
Kassmer SH, Jin H, Zhang PX, Bruscia EM, Heydari K, Lee JH, Kim CF, Kassmer SH, Krause DS. Very Small Embryonic‐Like Stem Cells from the Murine Bone Marrow Differentiate into Epithelial Cells of the Lung. Stem Cells 2013, 31: 2759-2766. PMID: 23681901, PMCID: PMC4536826, DOI: 10.1002/stem.1413.Peer-Reviewed Original ResearchConceptsEpithelial cellsSmall embryonic-like stem cellsLung epithelial cellsEmbryonic-like stem cellsStem/progenitor cellsStem cellsDonor miceHematopoietic stem/progenitor cellsBM cellsAdult BMBone marrowSmall embryonicNonhematopoietic cellsProgenitor cellsBroad differentiation potentialVSELsEngraftmentLungHigh rateNumerous reportsAdult stem cellsDifferentiation potentialCellsFirst reportReport
2012
Nonhematopoietic Cells are the Primary Source of Bone Marrow‐Derived Lung Epithelial Cells
Kassmer SH, Bruscia EM, Zhang P, Krause DS. Nonhematopoietic Cells are the Primary Source of Bone Marrow‐Derived Lung Epithelial Cells. Stem Cells 2012, 30: 491-499. PMID: 22162244, PMCID: PMC3725285, DOI: 10.1002/stem.1003.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacterial ProteinsBone Marrow CellsBone Marrow TransplantationCell SeparationEpithelial CellsGene ExpressionLuminescent ProteinsLungMiceMice, 129 StrainMice, Inbred C57BLMice, KnockoutMicroscopy, ConfocalPulmonary Surfactant-Associated Protein CRecombinant ProteinsSingle-Cell AnalysisConceptsLung epithelial cellsNonhematopoietic cellsBM cellsEpithelial cellsBone marrowLungs of miceType 2 pneumocytesNonhematopoietic stem cellsNonhematopoietic fractionAdult BMPrimitive stem cell populationNull miceProgenitor cellsMiceStem cell populationCell populationsMarrowStem cellsMultiple tissuesHematopoietic stemBMCellsPrevious studiesEngraftmentLung
2010
Detection of bone marrow–derived lung epithelial cells
Kassmer SH, Krause DS. Detection of bone marrow–derived lung epithelial cells. Experimental Hematology 2010, 38: 564-573. PMID: 20447442, PMCID: PMC2909593, DOI: 10.1016/j.exphem.2010.04.011.Peer-Reviewed Original ResearchConceptsMarrow-derived epithelial cellsBone marrow-derived cellsMarrow-derived cellsLung epithelial cellsEpithelial cellsBone marrow-derived epithelial cellsDonor bone marrow originBone marrow originBone marrow cellsBlood cell markersNormal tissue repairSpecific cell subsetsCell subsetsGastrointestinal tractTherapeutic benefitMarrow originMultiple organsEpithelial markersDefinitive dataCell markersMarrow cellsProtein expression patternsTissue repairEngraftmentLung
2008
Bone Marrow–derived Lung Epithelial Cells
Krause DS. Bone Marrow–derived Lung Epithelial Cells. Annals Of The American Thoracic Society 2008, 5: 699-702. PMID: 18684720, PMCID: PMC2645262, DOI: 10.1513/pats.200803-031aw.Peer-Reviewed Original ResearchConceptsMarrow-derived epithelial cellsEpithelial cellsBone marrow-derived cellsMarrow-derived cellsLung epithelial cellsClinical significanceEpithelial-specific genesMultiple organsAdult lungMarrow cellsFurther studiesMultiple mechanismsRecent dataCellsRecent studiesSignificant skepticismEngraftmentLungBone Marrow–derived Cells and Stem Cells in Lung Repair
Krause DS. Bone Marrow–derived Cells and Stem Cells in Lung Repair. Annals Of The American Thoracic Society 2008, 5: 323-327. PMID: 18403327, PMCID: PMC2645242, DOI: 10.1513/pats.200712-169dr.Peer-Reviewed Original ResearchConceptsMarrow-derived epithelial cellsEpithelial cellsBM cellsTissue injuryBone marrow-derived cellsBM-derived cellsMarrow-derived cellsPotential clinical utilityBronchiolar epithelial cellsType II pneumocytesLung damageTracheal epithelial cellsLung repairClinical utilityGI tractBone marrowTissue damagePeer-reviewed studiesNonhematopoietic cell typesBeneficial effectsPotential mechanismsTissue repairLungInjuryTissue microenvironment
2006
Engraftment of Marrow-derived Epithelial Cells
Herzog EL, Krause DS. Engraftment of Marrow-derived Epithelial Cells. Annals Of The American Thoracic Society 2006, 3: 691-695. PMID: 17065375, PMCID: PMC2647654, DOI: 10.1513/pats.200605-109sf.BooksThreshold of Lung Injury Required for the Appearance of Marrow‐Derived Lung Epithelia
Herzog EL, Van Arnam J, Hu B, Krause DS. Threshold of Lung Injury Required for the Appearance of Marrow‐Derived Lung Epithelia. Stem Cells 2006, 24: 1986-1992. PMID: 16868209, DOI: 10.1634/stemcells.2005-0579.Peer-Reviewed Original ResearchConceptsBone marrow-derived cellsBone marrow transplantationLung injuryMarrow transplantationLung epitheliumEngraftment of BMDCsLocal host factorsSex-mismatched bone marrow transplantationMarrow-derived cellsType II pneumocytesMyeloablative radiationLung damageHematopoietic chimerismEpithelial chimerismApparent injuryInjuryTransplantationHost factorsEpitheliumEpithelial cellsEpithelial phenotypeLungChimerismPneumocytesPhenotypic changes
2005
Engraftment of bone marrow-derived epithelial cells
Van Arnam JS, Herzog E, Grove J, Bruscia E, Ziegler E, Swenson S, Krause DS. Engraftment of bone marrow-derived epithelial cells. Stem Cell Reviews And Reports 2005, 1: 21-27. PMID: 17132871, DOI: 10.1385/scr:1:1:021.Peer-Reviewed Original ResearchConceptsBM-derived cellsEpithelial cellsBM transplantationBone marrow-derived epithelial cellsMarrow-derived epithelial cellsPreclinical mouse modelsType II pneumocytesHematopoietic systemGene therapyFalse-positive cellsGastrointestinal tractHost epithelial cellsMouse modelFemale recipientsPositive cellsBone marrowCre-lox systemTherapeutic potentialTherapeutic useTissue-specific markersTransplantationTherapyPotential gene therapy applicationsCellsHuman diseases
2002
Radiation pneumonitis in mice A severe injury model for pneumocyte engraftment from bone marrow
Theise ND, Henegariu O, Grove J, Jagirdar J, Kao PN, Crawford JM, Badve S, Saxena R, Krause DS. Radiation pneumonitis in mice A severe injury model for pneumocyte engraftment from bone marrow. Experimental Hematology 2002, 30: 1333-1338. PMID: 12423687, DOI: 10.1016/s0301-472x(02)00931-1.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkersBone Marrow TransplantationCell DifferentiationCell LineageEpithelial CellsFemaleGraft SurvivalIn Situ Hybridization, FluorescenceLungMaleMiceModels, AnimalPulmonary AlveoliPulmonary Surfactant-Associated Protein BRadiation ChimeraRadiation PneumonitisRNA, MessengerStem Cell TransplantationStem CellsY ChromosomeConceptsBone marrow transplantType II pneumocytesBone marrow cellsFemale miceLethal irradiationAge-matched male donorsWhole bone marrow transplantsMarrow cellsDay 5 posttransplantAlveolar lining cellsFluorescence-activated cell sorterSevere injury modelType I cellsAlveolar breakdownEntire alveoliRadiation pneumonitisB messenger RNAHistologic evidenceMarrow transplantAcute injuryMonth 2Injury modelLung tissueLining cellsBone marrow
2001
Multi-Organ, Multi-Lineage Engraftment by a Single Bone Marrow-Derived Stem Cell
Krause D, Theise N, Collector M, Henegariu O, Hwang S, Gardner R, Neutzel S, Sharkis S. Multi-Organ, Multi-Lineage Engraftment by a Single Bone Marrow-Derived Stem Cell. Cell 2001, 105: 369-377. PMID: 11348593, DOI: 10.1016/s0092-8674(01)00328-2.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CD34Antigens, LyBone Marrow CellsCell LineageCell MovementEpithelial CellsFemaleFluorescent DyesHematopoietic Stem Cell TransplantationHematopoietic Stem CellsHumansImmunohistochemistryIn Situ Hybridization, FluorescenceIntestine, SmallKeratinsLungMaleMembrane ProteinsMiceMice, KnockoutOrganic ChemicalsPulmonary SurfactantsStem CellsY ChromosomeConceptsLong-term repopulationSingle bone marrowMulti-lineage engraftmentAdult bone marrow cellsProperties of HSCHematopoietic stemSecondary hostsGenetic diseasesStem cellsBone marrow cellsExpression increasesDifferentiative capacityBone marrowEpithelial cellsSerial transplantationRare cellsTissue repairMarrow cellsCellsDifferentiationHostSecondary recipientsGI tractPhenotypeMarrow