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 recruitmentProteinAktPrior Influenza Infection Mitigates SARS-CoV-2 Disease in Syrian Hamsters
Di Pietro C, Haberman A, Lindenbach B, Smith P, Bruscia E, Allore H, Vander Wyk B, Tyagi A, Zeiss C. Prior Influenza Infection Mitigates SARS-CoV-2 Disease in Syrian Hamsters. Viruses 2024, 16: 246. PMID: 38400021, PMCID: PMC10891789, DOI: 10.3390/v16020246.Peer-Reviewed Original ResearchConceptsTransient gene expressionSARS-CoV-2Viral replication pathwayReplication pathwayAntiviral pathwaysEndemism patternsUpregulation of innateGene expressionQuantitative RT-PCRMitigated weight lossDual-infected animalsSARS-CoV-2 viral loadSARS-CoV-2 infectionSyrian hamstersSeasonal infection ratesSARS-CoV-2 inoculationLungs of animalsIndividual virusesSARS-CoV-2 diseaseUpper respiratory tractH1N1 infectionRT-PCRBronchoalveolar lavageViral loadCytokine levels
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 targetUpdate on Innate and Adaptive Immunity in Cystic Fibrosis
Bruscia E, Bonfield T. Update on Innate and Adaptive Immunity in Cystic Fibrosis. Clinics In Chest Medicine 2022, 43: 603-615. PMID: 36344069, DOI: 10.1016/j.ccm.2022.06.004.Peer-Reviewed Original ResearchConceptsChronic infectionCFTR modulator therapyRobust inflammatory responseCystic fibrosis pathophysiologyImmune dysregulationPatient ageExcessive inflammationModulator therapyLung microenvironmentLung infectionImmune mechanismsInflammatory responseAdaptive immunityMucociliary transportCF life expectancyCF lungCystic fibrosisInfectionLife expectancyImmunityCritical roleCurrent understandingMorbidityInflammationFibrosisRecruitment 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
Cystic Fibrosis Lung Immunity: The Role of the Macrophage
Bruscia EM, Bonfield TL. Cystic Fibrosis Lung Immunity: The Role of the Macrophage. Journal Of Innate Immunity 2016, 8: 550-563. PMID: 27336915, PMCID: PMC5089923, DOI: 10.1159/000446825.Peer-Reviewed Original ResearchConceptsLung homeostasisCystic fibrosis pathophysiologyTranscriptional shiftMortality of patientsEnvironmental cuesAdaptive immune networkModifier genesMΦ functionMajor morbidityExcessive inflammationMΦ phenotypeLung infectionCF lungCFTR dysfunctionMajor playersHomeostasisDiseaseMacrophagesIntrinsic changesGenesImmune networkPhenotypeMorbidityInflammationPatientsIncreased 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
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