Featured Publications
Macrophage migration inhibitory factor deficiency in chronic obstructive pulmonary disease
Sauler M, Leng L, Trentalange M, Haslip M, Shan P, Piecychna M, Zhang Y, Andrews N, Mannam P, Allore H, Fried T, Bucala R, Lee PJ. Macrophage migration inhibitory factor deficiency in chronic obstructive pulmonary disease. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2014, 306: l487-l496. PMID: 24441872, PMCID: PMC3949087, DOI: 10.1152/ajplung.00284.2013.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAge FactorsAgedAged, 80 and overAnimalsApoptosisCellular SenescenceCyclin-Dependent Kinase Inhibitor p16Cyclin-Dependent Kinase Inhibitor p21EmphysemaFemaleHumansIntramolecular OxidoreductasesLungMacrophage Migration-Inhibitory FactorsMaleMiceMice, Inbred C57BLMice, KnockoutMiddle AgedPulmonary Disease, Chronic ObstructiveReceptors, ImmunologicSmokeSmokingTobaccoTumor Suppressor Protein p53Young AdultConceptsChronic obstructive pulmonary diseaseMacrophage migration inhibitory factorPathogenesis of COPDDevelopment of COPDMIF receptor CD74Obstructive pulmonary diseasePulmonary diseaseWT miceReceptor CD74Role of MIFMacrophage migration inhibitory factor deficiencyMigration inhibitory factorNormal alveolar structureMo of ageWild-type controlsMIF concentrationsFormer smokersLung volumePlasma concentrationsSpontaneous emphysemaFactor deficiencyCigarette smokePleiotropic cytokineInhibitory factorAlveolar structuresEndothelial CD74 mediates macrophage migration inhibitory factor protection in hyperoxic lung injury
Sauler M, Zhang Y, Min J, Leng L, Shan P, Roberts S, Jorgensen WL, Bucala R, Lee PJ. Endothelial CD74 mediates macrophage migration inhibitory factor protection in hyperoxic lung injury. The FASEB Journal 2015, 29: 1940-1949. PMID: 25609432, PMCID: PMC4415022, DOI: 10.1096/fj.14-260299.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorLung endothelial cellsMurine lung endothelial cellsLung injuryEndothelial cellsProtective effectExogenous MIFCD74 deficient miceCD74-dependent mannerHours of hyperoxiaMIF receptor CD74Acute lung injuryHyperoxic lung injuryBronchoalveolar lavage proteinMigration inhibitory factorBronchoalveolar proteinMIF deficiencyMedian survivalEndothelial injuryWT miceAcute oxidative stressReceptor CD74Lavage proteinReceptor antagonistReceptor inhibitorsA functional macrophage migration inhibitory factor promoter polymorphism is associated with reduced diffusing capacity
Zhang C, Ramsey C, Berical A, Yu L, Leng L, McGinnis K, Song Y, Michael H, McCormack M, Allore H, Morris A, Crothers K, Bucala R, Lee P, Sauler M. A functional macrophage migration inhibitory factor promoter polymorphism is associated with reduced diffusing capacity. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2018, 316: l400-l405. PMID: 30520689, PMCID: PMC6397351, DOI: 10.1152/ajplung.00439.2018.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorChronic obstructive pulmonary diseaseMIF -794 CATTAbnormal diffusion capacityCigarette smoke exposureSmoke exposureAssociation of MIFDiffusion capacityMacrophage migration inhibitory factor (MIF) promoter polymorphismsPathogenesis of COPDChronic cigarette smoke exposureMultivariable logistic regression modelModifiable risk factorsObstructive pulmonary diseaseMigration inhibitory factorCross-sectional analysisLogistic regression modelsCommon genetic polymorphismsInnate immune genesAirflow obstructionMIF expressionCOPD severityPulmonary diseaseMIF allelesRisk factors
2022
MIF is a common genetic determinant of COVID-19 symptomatic infection and severity
Shin JJ, Fan W, Par-Young J, Piecychna M, Leng L, Israni-Winger K, Qing H, Gu J, Zhao H, Schulz WL, Unlu S, Kuster J, Young G, Liu J, Ko AI, Garcia A, Sauler M, Wisnewski AV, Young L, Orduña A, Wang A, Klementina O, Garcia AB, Hegyi P, Armstrong ME, Mitchell P, Ordiz DB, Garami A, Kang I, Bucala R. MIF is a common genetic determinant of COVID-19 symptomatic infection and severity. QJM 2022, 116: 205-212. PMID: 36222594, PMCID: PMC9620729, DOI: 10.1093/qjmed/hcac234.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorLow-expression MIF alleleCOVID-19 infectionMIF allelesCATT7 alleleHealthy controlsCOVID-19Serum macrophage migration inhibitory factorSymptomatic SARS-CoV-2 infectionHigher serum MIF levelsHigh-expression MIF allelesRetrospective case-control studySARS-CoV-2 infectionFunctional polymorphismsAvailable clinical characteristicsMultinational retrospective studySerum MIF levelsUninfected healthy controlsSymptomatic COVID-19Tertiary medical centerHealthy control subjectsCase-control studyMigration inhibitory factorCoronavirus disease 2019Common functional polymorphisms
2021
MIF but not MIF-2 recruits inflammatory macrophages in an experimental polymicrobial sepsis model
Tilstam PV, Schulte W, Holowka T, Kim BS, Nouws J, Sauler M, Piecychna M, Pantouris G, Lolis E, Leng L, Bernhagen J, Fingerle-Rowson G, Bucala R. MIF but not MIF-2 recruits inflammatory macrophages in an experimental polymicrobial sepsis model. Journal Of Clinical Investigation 2021, 131: e127171. PMID: 34850744, PMCID: PMC8631602, DOI: 10.1172/jci127171.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCytokinesDisease Models, AnimalFemaleFlow CytometryGene Expression ProfilingInflammationIntramolecular OxidoreductasesLeukocyte CountMacrophage Migration-Inhibitory FactorsMacrophagesMacrophages, PeritonealMaleMiceMice, Inbred C57BLMice, TransgenicPeritoneal LavagePhenotypeProtein BindingRNA-SeqSepsisSignal TransductionConceptsMacrophage migration inhibitory factorSmall peritoneal macrophagesLarge peritoneal macrophagesPolymicrobial sepsisPeritoneal macrophagesMIF receptor CD74MIF promoter polymorphismsMIF-2Migration inhibitory factorPolymicrobial sepsis modelMIF deficiencyAdoptive transferSeptic shockSurvival benefitInfectious insultsMIF antibodyExcessive inflammationInflammatory cytokinesReceptor CD74Sepsis modelProtective effectPeritoneal cavityDifferent infectionsPromoter polymorphismInflammatory macrophages
2020
Macrophage Migration Inhibitory Factor is not Associated with Sarcoidosis Susceptibility or Severity in Whites or Blacks
Odio CD, Miller EJ, Sauler M, Leng L, Piecychna M, Drake WP, Bucala R. Macrophage Migration Inhibitory Factor is not Associated with Sarcoidosis Susceptibility or Severity in Whites or Blacks. Sarcoidosis, Vasculitis, And Diffuse Lung Diseases 2020, 37: e2020003. PMID: 33264374, PMCID: PMC7690059, DOI: 10.36141/svdld.v37i3.9273.Peer-Reviewed Original ResearchMacrophage migration inhibitory factorMigration inhibitory factorHealthy controlsMacrophage migration inhibitory factor (MIF) promoter polymorphismsSarcoidosis severityInhibitory factorAlpha-1 antitrypsin deficiencyLarge North American cohortHigh expressionSarcoidosis susceptibilityNorth American cohortPulmonary sarcoidosisSarcoidosis patientsAutoimmune diseasesInflammatory cytokinesSarcoidosis phenotypesSarcoidosis StudyAntitrypsin deficiencyPromoter polymorphismAmerican cohortSarcoidosisSmall sample sizeSeverityC SNPPatientsDifferential regulation of macrophage activation by the MIF cytokine superfamily members MIF and MIF‐2 in adipose tissue during endotoxemia
Kim B, Tilstam PV, Arnke K, Leng L, Ruhl T, Piecychna M, Schulte W, Sauler M, Frueh FS, Storti G, Lindenblatt N, Giovanoli P, Pallua N, Bernhagen J, Bucala R. Differential regulation of macrophage activation by the MIF cytokine superfamily members MIF and MIF‐2 in adipose tissue during endotoxemia. The FASEB Journal 2020, 34: 4219-4233. PMID: 31961019, PMCID: PMC7060131, DOI: 10.1096/fj.201901511r.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorWhite adipose tissueAdipose tissue macrophagesAdipose tissueElevated macrophage migration inhibitory factorInflammatory cytokine macrophage migration inhibitory factorVisceral white adipose tissueCytokine macrophage migration inhibitory factorPro-inflammatory macrophage polarizationMIF family proteinsPro-inflammatory phenotypeAnti-inflammatory phenotypeMIF-2Migration inhibitory factorWild-type miceHuman adipose tissueMurine endotoxemia modelMIF cytokineMIF deficiencySystemic inflammationDifferential regulationHealthy patientsEndotoxemia modelPeritoneal fluidLeading cause
2018
Endothelial cell‐secreted MIF reduces pericyte contractility and enhances neutrophil extravasation
Pellowe AS, Sauler M, Hou Y, Merola J, Liu R, Calderon B, Lauridsen HM, Harris MR, Leng L, Zhang Y, Tilstam PV, Pober JS, Bucala R, Lee PJ, Gonzalez AL. Endothelial cell‐secreted MIF reduces pericyte contractility and enhances neutrophil extravasation. The FASEB Journal 2018, 33: 2171-2186. PMID: 30252532, PMCID: PMC6338650, DOI: 10.1096/fj.201800480r.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorNeutrophil transmigrationNeutrophil extravasationPericyte contractilitySelective deletionMIF knockout miceAcute lung injuryMigration inhibitory factorHuman neutrophil transmigrationMyosin light chain phosphorylationLung injuryNeutrophil infiltrationBronchoalveolar lavageInflammatory disordersKnockout miceInhibitory factorMicro-ELISAContractilityLight chain phosphorylationPhosphorylated myosin light chainEndothelial cellsBarrier functionExtravasationPericytesParacrine signals
2017
Complexity of macrophage migration inhibitory factor (MIF) and other angiogenic biomarkers profiling in pulmonary arterial hypertension
Marshall JD, Sauler M, Tonelli A, Rao Y, Bucala R, Lee PJ, Fares WH. Complexity of macrophage migration inhibitory factor (MIF) and other angiogenic biomarkers profiling in pulmonary arterial hypertension. Pulmonary Circulation 2017, 7: 730-733. PMID: 28714356, PMCID: PMC5841895, DOI: 10.1177/2045893217724141.Peer-Reviewed Original ResearchMacrophage migration inhibitory factorMigration inhibitory factorInhibitory factorPulmonary arterial hypertension patientsPulmonary arterial hypertensionArterial hypertension patientsArterial hypertensionHypertension patientsAngiogenic biomarkersAngiogenic factorsSignificant positive correlationBiomarkersPositive correlationRegulation roleHypertensionPatientsFactorsPathobiologyMIF and Pulmonary Disease
Baker T, Lee P, Sauler M. MIF and Pulmonary Disease. Progress In Inflammation Research 2017, 135-144. DOI: 10.1007/978-3-319-52354-5_8.ChaptersMacrophage migration inhibitory factorPulmonary diseaseRole of MIFMigration inhibitory factorInnate immune responseLung surface areaLung diseaseImmune responseProtective roleInhibitory factorMultifunctional cytokineLungOxidative stressDiseaseCritical regulatorExternal toxinsGas exchangeCytokinesPathogenesis
2016
MIF allele-dependent regulation of the MIF coreceptor CD44 and role in rheumatoid arthritis
Yoo SA, Leng L, Kim BJ, Du X, Tilstam PV, Kim KH, Kong JS, Yoon HJ, Liu A, Wang T, Song Y, Sauler M, Bernhagen J, Ritchlin CT, Lee P, Cho CS, Kim WU, Bucala R. MIF allele-dependent regulation of the MIF coreceptor CD44 and role in rheumatoid arthritis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: e7917-e7926. PMID: 27872288, PMCID: PMC5150393, DOI: 10.1073/pnas.1612717113.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorHigh-expression MIF allelesJoint destructionRheumatoid arthritisMIF allelesProgressive joint destructionInvasive phenotypeFibroblast-like synoviocytesMigration inhibitory factorJoint erosionsMIF receptorAutoimmune responseMIF pathwaySynovial fibroblastsCell surface CD74Autocrine pathwayCD44 expressionInhibitory factorPharmacologic inhibitionTumor invasionArthritisInvasive propertiesCD44 receptorCD44Receptor complexThe clinical significance of the MIF homolog d-dopachrome tautomerase (MIF-2) and its circulating receptor (sCD74) in burn
Kim BS, Stoppe C, Grieb G, Leng L, Sauler M, Assis D, Simons D, Boecker AH, Schulte W, Piecychna M, Hager S, Bernhagen J, Pallua N, Bucala R. The clinical significance of the MIF homolog d-dopachrome tautomerase (MIF-2) and its circulating receptor (sCD74) in burn. Burns 2016, 42: 1265-1276. PMID: 27209369, PMCID: PMC5010466, DOI: 10.1016/j.burns.2016.02.005.Peer-Reviewed Original ResearchConceptsTotal body surface areaMacrophage migration inhibitory factorSerum levelsClinical significanceCytokine macrophage migration inhibitory factorEarly post-burn periodPrediction of sepsisBody surface areaMigration inhibitory factorPost-burn periodBurn severity indexDopachrome tautomeraseClinical outcomesBurn patientsReceptor CD74Healthy controlsBurn injuryEarly predictorMember DPatientsPotential biomarkersCD74Inhibitory factorSoluble CD74Severity IndexTranscription factor ICBP90 regulates the MIF promoter and immune susceptibility locus
Yao J, Leng L, Sauler M, Fu W, Zheng J, Zhang Y, Du X, Yu X, Lee P, Bucala R. Transcription factor ICBP90 regulates the MIF promoter and immune susceptibility locus. Journal Of Clinical Investigation 2016, 126: 732-744. PMID: 26752645, PMCID: PMC4731159, DOI: 10.1172/jci81937.Peer-Reviewed Original ResearchMeSH KeywordsArthritis, RheumatoidCCAAT-Enhancer-Binding ProteinsGenetic LociGenetic Predisposition to DiseaseHumansIntramolecular OxidoreductasesJurkat CellsMacrophage Migration-Inhibitory FactorsMicrosatellite RepeatsPolymorphism, GeneticPromoter Regions, GeneticTranscription, GeneticUbiquitin-Protein LigasesConceptsTranscription factorsMacrophage migration inhibitory factorWhole-genome transcription analysisOligonucleotide affinity chromatographyLength-dependent mannerTranscriptional regulationFunctional insightsTranscription analysisNuclear proteinsImmune response genesPolymorphic lociMIF promoterResponse genesNuclear lysatesKey regulatorHigher mRNA levelsMajor proteinsSusceptibility lociTranscriptionCytokine macrophage migration inhibitory factorLociExpression levelsCommon allelesMigration inhibitory factorMicrosatellite polymorphism
2015
Role of macrophage migration inhibitory factor in age-related lung disease
Sauler M, Bucala R, Lee PJ. Role of macrophage migration inhibitory factor in age-related lung disease. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2015, 309: l1-l10. PMID: 25957294, PMCID: PMC4491511, DOI: 10.1152/ajplung.00339.2014.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsMacrophage migration inhibitory factorAge-related lung diseaseMigration inhibitory factorLung diseaseInhibitory factorChronic obstructive lung diseaseChronic lung diseaseObstructive lung diseaseCommon respiratory disorderPulmonary fibrosisClinical manifestationsProinflammatory cytokinesLung cancerRespiratory disordersImmune systemVariant allelesDiseaseHost factorsSuch diseasesPotent upstream regulatorUpstream regulatorPneumoniaFibrosisBody of literatureCytokines