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 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 understandingMorbidityInflammationFibrosisEmerging Concepts in Defective Macrophage Phagocytosis in Cystic Fibrosis
Jaganathan D, Bruscia EM, Kopp BT. Emerging Concepts in Defective Macrophage Phagocytosis in Cystic Fibrosis. International Journal Of Molecular Sciences 2022, 23: 7750. PMID: 35887098, PMCID: PMC9319215, DOI: 10.3390/ijms23147750.Peer-Reviewed Original ResearchMeSH KeywordsCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorHumansInflammationMacrophagesPhagocytosisConceptsPhagosome formationCystic fibrosis transmembrane conductance regulator (CFTR) geneTransmembrane conductance regulator geneInnate immunityTissue homeostasisRegulator geneMutant CFTRCF macrophagesCystic fibrosisPhagocytic mechanismsPathogenic microbesAdaptive immune systemDefective macrophage phagocytosisCFTRCurrent understandingTherapeutic developmentCentral roleMacrophage phagocytosisCFTR modulatorsPhagocytic cellsPhagocytosisNew therapeutic developmentsMacrophages contributesLung functionChronic inflammationRecruitment 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
2020
Single-Cell Transcriptional Archetypes of Airway Inflammation in Cystic Fibrosis.
Schupp JC, Khanal S, Gomez JL, Sauler M, Adams TS, Chupp GL, Yan X, Poli S, Zhao Y, Montgomery RR, Rosas IO, Dela Cruz CS, Bruscia EM, Egan ME, Kaminski N, Britto CJ. Single-Cell Transcriptional Archetypes of Airway Inflammation in Cystic Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2020, 202: 1419-1429. PMID: 32603604, PMCID: PMC7667912, DOI: 10.1164/rccm.202004-0991oc.Peer-Reviewed Original ResearchConceptsCF lung diseaseHealthy control subjectsImmune dysfunctionLung diseaseCystic fibrosisControl subjectsSputum cellsAbnormal chloride transportLung mononuclear phagocytesInnate immune dysfunctionDivergent clinical coursesImmune cell repertoireMonocyte-derived macrophagesCF monocytesAirway inflammationClinical courseProinflammatory featuresCell survival programInflammatory responseTissue injuryCell repertoireImmune functionTranscriptional profilesAlveolar macrophagesMononuclear phagocytes
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 networkPhenotypeMorbidityInflammationPatients
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
2014
SRF is required for neutrophil migration in response to inflammation
Taylor A, Tang W, Bruscia EM, Zhang PX, Lin A, Gaines P, Wu D, Halene S. SRF is required for neutrophil migration in response to inflammation. Blood 2014, 123: 3027-3036. PMID: 24574460, PMCID: PMC4014845, DOI: 10.1182/blood-2013-06-507582.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonActinsAnimalsBlotting, WesternCell AdhesionCell MovementChemokinesGene ExpressionInflammationIntegrinsMiceMice, KnockoutMice, TransgenicMicroscopy, ConfocalNeutrophilsN-Formylmethionine Leucyl-PhenylalaninePolymerizationReverse Transcriptase Polymerase Chain ReactionSerum Response FactorSignal TransductionConceptsKO neutrophilsNeutrophil functionNormal neutrophil numbersSerum response factorSites of inflammationRole of SRFLoss of SRFNeutrophil numbersNeutrophil migrationMalignant processNeutrophilsCytokine stimuliChemokine gradientsCell functionExpression levelsIntegrin expression levelsInflammationMicePrimary defenseMegakaryocyte maturationNormal cell functionVivoCellular adhesionMaster regulatorIntegrin activation
2013
Reduced Caveolin-1 Promotes Hyperinflammation due to Abnormal Heme Oxygenase-1 Localization in Lipopolysaccharide-Challenged Macrophages with Dysfunctional Cystic Fibrosis Transmembrane Conductance Regulator
Zhang PX, Murray TS, Villella VR, Ferrari E, Esposito S, D'Souza A, Raia V, Maiuri L, Krause DS, Egan ME, Bruscia EM. Reduced Caveolin-1 Promotes Hyperinflammation due to Abnormal Heme Oxygenase-1 Localization in Lipopolysaccharide-Challenged Macrophages with Dysfunctional Cystic Fibrosis Transmembrane Conductance Regulator. The Journal Of Immunology 2013, 190: 5196-5206. PMID: 23606537, PMCID: PMC3711148, DOI: 10.4049/jimmunol.1201607.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAnimalsCaveolin 1Cells, CulturedChildChild, PreschoolCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorFemaleHeme Oxygenase-1HumansInflammationLipopolysaccharidesLung DiseasesMacrophagesMaleMembrane ProteinsMiceMice, KnockoutNasal PolypsReactive Oxygen SpeciesSignal TransductionToll-Like Receptor 4Young AdultConceptsCav-1 expressionHeme oxygenase-1Dysfunctional cystic fibrosis transmembrane conductance regulatorCystic fibrosis transmembrane conductance regulatorCell surfaceFibrosis transmembrane conductance regulatorProtein caveolin-1Cellular redox statusCell surface localizationCellular oxidative stateTransmembrane conductance regulatorHO-1 enzymePositive feed-forward loopCystic fibrosis macrophagesNegative regulatorCaveolin-1Conductance regulatorCell survivalHO-1 deliverySurface localizationRedox statusMΦ responsesHO-1/CO pathwayPathwayPotential target
2012
Innate immunity in cystic fibrosis lung disease
Hartl D, Gaggar A, Bruscia E, Hector A, Marcos V, Jung A, Greene C, McElvaney G, Mall M, Döring G. Innate immunity in cystic fibrosis lung disease. Journal Of Cystic Fibrosis 2012, 11: 363-382. PMID: 22917571, DOI: 10.1016/j.jcf.2012.07.003.Peer-Reviewed Original ResearchConceptsLung diseaseCF lung diseaseInnate immunityChronic infective lung diseaseNovel immune-targeted therapiesCystic fibrosis lung diseasePulmonary immune responseChronic lung diseaseImmune-targeted therapiesPro-inflammatory cascadeInfective lung diseaseInnate immune regulationInnate immune systemCystic fibrosis patientsPotential clinical relevanceEpithelial dysfunctionLeukocyte recruitmentImmune regulationImmune responseAdaptive immunityClinical relevanceFibrosis patientsImmune systemDiseaseImmunity
2011
Abnormal Trafficking and Degradation of TLR4 Underlie the Elevated Inflammatory Response in Cystic Fibrosis
Bruscia EM, Zhang PX, Satoh A, Caputo C, Medzhitov R, Shenoy A, Egan ME, Krause DS. Abnormal Trafficking and Degradation of TLR4 Underlie the Elevated Inflammatory Response in Cystic Fibrosis. The Journal Of Immunology 2011, 186: 6990-6998. PMID: 21593379, PMCID: PMC3111054, DOI: 10.4049/jimmunol.1100396.Peer-Reviewed Original Research