Featured Publications
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
2024
Downregulation of adipose LPL by PAR2 contributes to the development of hypertriglyceridemia
Huang Y, Chen L, Li L, Qi Y, Tong H, Wu H, Xu J, Leng L, Cheema S, Sun G, Xia Z, McGuire J, Rodrigues B, Young L, Bucala R, Qi D. Downregulation of adipose LPL by PAR2 contributes to the development of hypertriglyceridemia. JCI Insight 2024, 9: e173240. PMID: 38973609, PMCID: PMC11383372, DOI: 10.1172/jci.insight.173240.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorDevelopment of hypertriglyceridemiaWhite adipose tissueAdipose LPLPAR2 expressionLevels of macrophage migration inhibitory factorElevated plasma TG levelsLPL expressionLipoprotein lipaseIncrease PAR2 expressionPlasma MIF levelsPlasma TG levelsMigration inhibitory factorPalmitic acid dietInhibited Akt phosphorylationMIF levelsLipoprotein lipase geneTG levelsObese humansPlasma TGHypertriglyceridemiaAkt phosphorylationLipid storageInhibitory factorAdipose tissueMacrophage Migration Inhibitory Factor (MIF) and D-Dopachrome Tautomerase (DDT): Pathways to Tumorigenesis and Therapeutic Opportunities
Valdez C, Sánchez-Zuno G, Bucala R, Tran T. Macrophage Migration Inhibitory Factor (MIF) and D-Dopachrome Tautomerase (DDT): Pathways to Tumorigenesis and Therapeutic Opportunities. International Journal Of Molecular Sciences 2024, 25: 4849. PMID: 38732068, PMCID: PMC11084905, DOI: 10.3390/ijms25094849.Peer-Reviewed Original ResearchConceptsInhibition of MIFResponse to infectionNon-canonical signaling pathwaysClinical studiesCancer patientsClinical trialsInflammatory cytokinesDriving tumorigenesisClinical explorationCancer typesCancerDual inhibitionTherapeutic targetIn vivoIn vitroSignaling pathwayMIFAntitumor candidateBinding partnersMIF-Modulated Spinal Proteins Associated with Persistent Bladder Pain: A Proteomics Study
Ye S, Agalave N, Ma F, Mahmood D, Al-Grety A, Khoonsari P, Leng L, Svensson C, Bucala R, Kultima K, Vera P. MIF-Modulated Spinal Proteins Associated with Persistent Bladder Pain: A Proteomics Study. International Journal Of Molecular Sciences 2024, 25: 4484. PMID: 38674069, PMCID: PMC11050327, DOI: 10.3390/ijms25084484.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, Differentiation, B-LymphocyteCystitis, InterstitialDisease Models, AnimalFemaleHistocompatibility Antigens Class IIHyperalgesiaIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsMiceProteomicsReceptors, CXCR4Receptors, ImmunologicSpinal CordUrinary BladderConceptsMacrophage migration inhibitory factorProtease activated receptor 4C-X-C chemokine receptor type 4Bladder hyperalgesiaBladder painSpinal proteinsMIF receptor CD74MIF antagonismL6-S1 spinal segmentsSpinal mechanismsInterstitial cystitis/bladder pain syndromeMIF receptorSeparate groups of miceChemokine receptor type 4Associated with reliefGroups of miceC-X-CMigration inhibitory factorChanges compared to controlsBladder inflammationPain syndromeFemale miceNo significant changesSham i.Receptor 4IL-1 receptor 1 signaling shapes the development of viral antigen-specific CD4+ T cell responses following COVID-19 mRNA vaccination
Park H, Shin M, Shin J, Kim H, Kang B, Par-Young J, Unlu S, Afinogenova Y, Catanzaro J, Young J, Kim M, Lee S, Jeon S, You S, Racke M, Bucala R, Kang I. IL-1 receptor 1 signaling shapes the development of viral antigen-specific CD4+ T cell responses following COVID-19 mRNA vaccination. EBioMedicine 2024, 103: 105114. PMID: 38640835, PMCID: PMC11041015, DOI: 10.1016/j.ebiom.2024.105114.Peer-Reviewed Original ResearchConceptsCD4<sup>+</sup> T cellsCOVID-19 mRNA vaccinesAntigen-specific CD4<sup>+</sup> T cell responsesT cell responsesPrimary antibody deficiencyCD4<sup>+</sup> T cell responsesT cellsIL-1R1MRNA vaccinesIL-1IgG antibodiesAntigen-specific CD4<sup>+</sup> T cellsCD4+ T cell responsesLevels of IL-1R1Human CD4<sup>+</sup> T cellsIL-1 receptor 1Healthy individualsDose of COVID-19 mRNA vaccineAntigen-specific CD4IL-1R1 expressionT cell immunityRepetitive antigenic stimulationCytokines interleukin (IL)-1Immune response to virusesExpression of IL-1R1
2023
Macrophage migration inhibitory factor (MIF) and its homolog D-dopachrome tautomerase (D-DT) are significant promotors of UVB- but not chemically induced non-melanoma skin cancer
Huth S, Huth L, Heise R, Marquardt Y, Lopopolo L, Piecychna M, Boor P, Fingerle-Rowson G, Kapurniotu A, Yazdi A, Bucala R, Bernhagen J, Baron J. Macrophage migration inhibitory factor (MIF) and its homolog D-dopachrome tautomerase (D-DT) are significant promotors of UVB- but not chemically induced non-melanoma skin cancer. Scientific Reports 2023, 13: 11611. PMID: 37464010, PMCID: PMC10354066, DOI: 10.1038/s41598-023-38748-9.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorNon-melanoma skin cancerD-DTSkin cancerRecombinant macrophage migration inhibitory factorUVB irradiationAcute UVB irradiationPrevention of photocarcinogenesisMigration inhibitory factorAccumulation of macrophagesAdditive protective effectChronic UVB irradiationDouble knockout micePotential therapeutic targetMacrophage accumulationCommon cancerPathophysiological roleProtective effectSkin tumorsKnockout miceTherapeutic targetInhibitory factorGenetic deletionCytokinesCancerUrothelial Oxidative Stress and ERK Activation Mediate HMGB1-Induced Bladder Pain
Ye S, Mahmood D, Ma F, Leng L, Bucala R, Vera P. Urothelial Oxidative Stress and ERK Activation Mediate HMGB1-Induced Bladder Pain. Cells 2023, 12: 1440. PMID: 37408274, PMCID: PMC10217556, DOI: 10.3390/cells12101440.Peer-Reviewed Original ResearchConceptsHigh mobility group box 1Macrophage migration inhibitory factorBladder painOxidative stressDisulfide HMGB1Mobility group box 1MIF-deficient miceNovel potential therapeutic strategyMigration inhibitory factorGroup box 1Potential therapeutic strategyOxidative stress productionN-acetylcysteine amideERK activationIntravesical treatmentMicturition volumeMicturition parametersReceptor 4Mechanical thresholdPainTherapeutic strategiesBox 1Bladder tissueInhibitory factorWestern blot
2022
“Near Cure” treatment of severe acute EAE in MIF-1-deficient female and male mice with a bifunctional MHCII-derived molecular construct
Vandenbark AA, Meza-Romero R, Wiedrick J, Gerstner G, Seifert H, Kent G, Piechycna M, Benedek G, Bucala R, Offner H. “Near Cure” treatment of severe acute EAE in MIF-1-deficient female and male mice with a bifunctional MHCII-derived molecular construct. Cellular Immunology 2022, 378: 104561. PMID: 35738135, PMCID: PMC9714992, DOI: 10.1016/j.cellimm.2022.104561.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisAcute experimental autoimmune encephalomyelitisDRα1-MOG-35Multiple sclerosisMIF-1EAE scoresMale miceMIF-2Severe diseaseMacrophage migration inhibitory factorClinical EAE scoresMIF-deficient micePeripheral inflammatory cellsMigration inhibitory factorSpinal cord tissueT cell activationSex-dependent differencesEAE severityAutoimmune encephalomyelitisSerum levelsTreatment of WTInflammatory cellsFemale miceClinical signsCord tissueInterleukin-17 Contributes to Chikungunya Virus-Induced Disease
Liu X, Poo YS, Alves JC, Almeida RP, Mostafavi H, Tang PCH, Bucala R, Teixeira MM, Taylor A, Zaid A, Mahalingam S. Interleukin-17 Contributes to Chikungunya Virus-Induced Disease. MBio 2022, 13: e00289-22. PMID: 35254128, PMCID: PMC9040832, DOI: 10.1128/mbio.00289-22.Peer-Reviewed Original ResearchConceptsIL-17Chikungunya virusCHIKV infectionRheumatoid arthritisIL-17A-deficient miceIL-17-deficient miceInterleukin-17 ContributesSpecific antiviral drugsWild-type miceIL-17 signalingAlphaviral arthritidesIL-17AIL-23Neutrophil infiltrationPsoriatic arthritisArthritic inflammationIL-21Acute phaseIL-22Interleukin-17Chronic phaseIL-6Tissue infiltratesTissue inflammationDisease patientsMacrophage migration inhibitory factor regulates specific innate immune sensor responses in gingival epithelial cells
Kantrong N, Chang AM, Bamashmous S, Hajjar AM, Bucala RJ, Darveau RP. Macrophage migration inhibitory factor regulates specific innate immune sensor responses in gingival epithelial cells. The Journal Of Periodontology 2022, 93: 1940-1950. PMID: 35100435, DOI: 10.1002/jper.21-0598.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorGingival epithelial cellsIL-8/CXCL8Migration inhibitory factorGingival tissuesJunctional epitheliumGingival epitheliumRole of MIFInhibitory factorMIF KO miceEpithelial cellsExpression of TLR4Healthy gingival tissuesToll-like receptorsInterleukin-1 receptorRepertoire of receptorsOral healthNeutrophil chemoattractantIL-1R1IL-1R2Neutrophil regulationKO micePeriodontal tissuesIL-1ROral homeostasisCD74 ablation rescues type 2 diabetes mellitus-induced cardiac remodeling and contractile dysfunction through pyroptosis-evoked regulation of ferroptosis
Chen L, Yin Z, Qin X, Zhu X, Chen X, Ding G, Sun D, Wu NN, Fei J, Bi Y, Zhang J, Bucala R, Ren J, Zheng Q. CD74 ablation rescues type 2 diabetes mellitus-induced cardiac remodeling and contractile dysfunction through pyroptosis-evoked regulation of ferroptosis. Pharmacological Research 2022, 176: 106086. PMID: 35033649, DOI: 10.1016/j.phrs.2022.106086.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsAntigens, Differentiation, B-LymphocyteCell LineDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 2FemaleFerroptosisGene ExpressionHistocompatibility Antigens Class IIHumansMacrophage Migration-Inhibitory FactorsMaleMice, KnockoutMiddle AgedMyocardial ContractionMyocardiumNLR Family, Pyrin Domain-Containing 3 ProteinOxidative StressOxygen ConsumptionPyroptosisRatsVentricular RemodelingConceptsHigh glucose/high fatMacrophage migration inhibitory factorCardiac remodelingContractile dysfunctionCell death domainGene Ontology termsInhibitors of MIFRecombinant macrophage migration inhibitory factorCytokine macrophage migration inhibitory factorType 2 diabetes mellitusOntology termsDeath domainLipid peroxidationGlobal metabolic defectsKEGG analysisPlasma MIF levelsInjection of streptozotocinMitochondrial defectsHigh-fat dietMigration inhibitory factorInhibitor of NLRP3Cell deathPrecise interplayMitochondrial dysfunctionCognate receptors
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 macrophagesMacrophage migration inhibitory factor exerts pro‐proliferative and anti‐apoptotic effects via CD74 in murine hepatocellular carcinoma
Wirtz TH, Saal A, Bergmann I, Fischer P, Heinrichs D, Brandt EF, Koenen MT, Djudjaj S, Schneider KM, Boor P, Bucala R, Weiskirchen R, Bernhagen J, Trautwein C, Berres M. Macrophage migration inhibitory factor exerts pro‐proliferative and anti‐apoptotic effects via CD74 in murine hepatocellular carcinoma. British Journal Of Pharmacology 2021, 178: 4452-4467. PMID: 34250589, DOI: 10.1111/bph.15622.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorMIF/CD74 axisMigration inhibitory factorHepatocellular carcinomaRole of MIFInhibitory factorReduced tumor burdenAnti-CD74 antibodiesNew pharmacological therapiesDEN/CClDifferent inflammatory diseasesChemokine-like proteinTherapy-induced cell deathMurine hepatocellular carcinomaPro-tumorigenic roleAnti-apoptotic effectsCarbon tetrachloride modelTherapy-induced apoptosisMIF knockoutMIF receptorPharmacological therapyTumor burdenControl miceReceptor CD74CD74 antibodyIntravesical CD74 and CXCR4, macrophage migration inhibitory factor (MIF) receptors, mediate bladder pain
Ye S, Ma F, Mahmood DFD, Meyer-Siegler KL, Menard RE, Hunt DE, Leng L, Bucala R, Vera PL. Intravesical CD74 and CXCR4, macrophage migration inhibitory factor (MIF) receptors, mediate bladder pain. PLOS ONE 2021, 16: e0255975. PMID: 34424927, PMCID: PMC8382170, DOI: 10.1371/journal.pone.0255975.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorHigh mobility group box 1Bladder painMIF receptorHMGB1 releaseBladder hyperalgesiaMobility group box 1MIF receptor CD74Migration inhibitory factorGroup box 1Primary urothelial cellsInhibitory factor receptorWarrants further investigationCD74 receptorReceptor CD74Micturition parametersReceptor antagonistReceptor 4Box 1PainInhibitory factorHyperalgesiaCD74Urothelial cellsNovel targetRole of MIF in coordinated expression of hepatic chemokines in patients with alcohol-associated hepatitis
Poulsen KL, Fan X, Kibler CD, Huang E, Wu X, McMullen MR, Leng L, Bucala R, Ventura-Cots M, Argemi J, Bataller R, Nagy LE. Role of MIF in coordinated expression of hepatic chemokines in patients with alcohol-associated hepatitis. JCI Insight 2021, 6: e141420. PMID: 33945507, PMCID: PMC8262327, DOI: 10.1172/jci.insight.141420.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorAlcohol-associated hepatitisChemokine expressionHealthy controlsLiver diseaseRole of MIFMIF KO miceChronic liver diseaseCytokines/chemokinesMigration inhibitory factorUpstream regulatorChemokine signatureChemokine CCL20WT miceCultured hepatocytesMultiple chemokinesChemokine systemInflammatory responseChemokine membersNovel therapiesEthanol feedingPatientsChemokine familyChemokinesInhibitory factor17‐a‐estradiol late in life extends lifespan in aging UM‐HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex
Harrison DE, Strong R, Reifsnyder P, Kumar N, Fernandez E, Flurkey K, Javors MA, Lopez‐Cruzan M, Macchiarini F, Nelson JF, Markewych A, Bitto A, Sindler AL, Cortopassi G, Kavanagh K, Leng L, Bucala R, Rosenthal N, Salmon A, Stearns TM, Bogue M, Miller RA. 17‐a‐estradiol late in life extends lifespan in aging UM‐HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex. Aging Cell 2021, 20: e13328. PMID: 33788371, PMCID: PMC8135004, DOI: 10.1111/acel.13328.Peer-Reviewed Original ResearchCD74 is a regulator of hematopoietic stem cell maintenance
Becker-Herman S, Rozenberg M, Hillel-Karniel C, Gil-Yarom N, Kramer M, Barak A, Sever L, David K, Radomir L, Lewinsky H, Levi M, Friedlander G, Bucala R, Peled A, Shachar I. CD74 is a regulator of hematopoietic stem cell maintenance. PLOS Biology 2021, 19: e3001121. PMID: 33661886, PMCID: PMC7963458, DOI: 10.1371/journal.pbio.3001121.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsAntigens, Differentiation, B-LymphocyteBone Marrow CellsBone Marrow TransplantationCell LineageFemaleHealthy VolunteersHematopoietic Stem CellsHistocompatibility Antigens Class IIHumansIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsMaleMiceMice, Inbred C57BLSignal TransductionConceptsMacrophage migration inhibitory factorHematopoietic stem cellsBone marrowCytokine macrophage migration inhibitory factorMigration inhibitory factorNumber of HSPCsTransplant protocolsCD18 expressionClinical transplantationInduced SurvivalCD74Inhibitory factorBM nicheCell surface receptorsSelf-renewal propertiesClinical insightsProgenitor cellsBlood cell lineagesSurface receptorsStem cellsHematopoietic stemCell lineagesCellsUndifferentiated cellsHematopoietic stem cell maintenanceHsp90-stabilized MIF supports tumor progression via macrophage recruitment and angiogenesis in colorectal cancer
Klemke L, De Oliveira T, Witt D, Winkler N, Bohnenberger H, Bucala R, Conradi LC, Schulz-Heddergott R. Hsp90-stabilized MIF supports tumor progression via macrophage recruitment and angiogenesis in colorectal cancer. Cell Death & Disease 2021, 12: 155. PMID: 33542244, PMCID: PMC7862487, DOI: 10.1038/s41419-021-03426-z.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenic ProteinsAnimalsAntigens, Differentiation, B-LymphocyteAntineoplastic AgentsColitis-Associated NeoplasmsDisease Models, AnimalFemaleHCT116 CellsHEK293 CellsHistocompatibility Antigens Class IIHSP90 Heat-Shock ProteinsHumansInflammation MediatorsIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsMaleMice, Inbred C57BLMice, KnockoutNeovascularization, PathologicOrganoidsProtein StabilitySignal TransductionTumor BurdenTumor-Associated MacrophagesConceptsMacrophage migration inhibitory factorMIF levelsMacrophage recruitmentAction of MIFColitis-associated colorectal cancer (CAC) mouse modelTumor growthTumor progressionFunction of MIFColorectal cancer mouse modelHigher MIF levelsHost inflammatory pathwaysTumor-specific functionsEpithelial cellsShorter overall survivalCRC tumor progressionClinical correlation studiesMigration inhibitory factorCRC tumor growthCancer mouse modelWild-type organoidsTumor epithelial cellsHSP90 inhibitor treatmentCD74 expressionOverall survivalCRC patientsUnexpected Pro-Fibrotic Effect of MIF in Non-Alcoholic Steatohepatitis Is Linked to a Shift in NKT Cell Populations
Heinrichs D, Brandt EF, Fischer P, Köhncke J, Wirtz TH, Guldiken N, Djudjaj S, Boor P, Kroy D, Weiskirchen R, Bucala R, Wasmuth HE, Strnad P, Trautwein C, Bernhagen J, Berres ML. Unexpected Pro-Fibrotic Effect of MIF in Non-Alcoholic Steatohepatitis Is Linked to a Shift in NKT Cell Populations. Cells 2021, 10: 252. PMID: 33525493, PMCID: PMC7918903, DOI: 10.3390/cells10020252.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkersCell PolarityDietDisease ProgressionFibrosisGene Expression RegulationHepatic Stellate CellsHepatocytesHumansLiverMacrophage Migration-Inhibitory FactorsMaleMice, Inbred C57BLModels, BiologicalNatural Killer T-CellsNon-alcoholic Fatty Liver DiseaseReceptors, ImmunologicConceptsMacrophage migration inhibitory factorNon-alcoholic fatty liver diseaseNAFLD progressionLiver fibrogenesisNKT cell populationNKT cell subpopulationsChronic liver injuryFatty liver diseaseNon-alcoholic steatohepatitisAnti-fibrotic propertiesPro-fibrotic effectsMigration inhibitory factorPleiotropic inflammatory cytokineLiver injury modelPro-fibrotic phenotypeMIF expressionMurine resultsNASH patientsNKT cellsLiver injuryLiver diseaseFibrosis markersInflammatory cytokinesDiet feedingInjury model
2020
Designed CXCR4 mimic acts as a soluble chemokine receptor that blocks atherogenic inflammation by agonist-specific targeting
Kontos C, El Bounkari O, Krammer C, Sinitski D, Hille K, Zan C, Yan G, Wang S, Gao Y, Brandhofer M, Megens RTA, Hoffmann A, Pauli J, Asare Y, Gerra S, Bourilhon P, Leng L, Eckstein HH, Kempf WE, Pelisek J, Gokce O, Maegdefessel L, Bucala R, Dichgans M, Weber C, Kapurniotu A, Bernhagen J. Designed CXCR4 mimic acts as a soluble chemokine receptor that blocks atherogenic inflammation by agonist-specific targeting. Nature Communications 2020, 11: 5981. PMID: 33239628, PMCID: PMC7689490, DOI: 10.1038/s41467-020-19764-z.Peer-Reviewed Original ResearchMeSH KeywordsAgedAnimalsAntigens, CDAtherosclerosisBinding SitesCarotid Artery, CommonChemokine CXCL12Crystallography, X-RayDisease Models, AnimalDrug DesignDrug Evaluation, PreclinicalEndarterectomy, CarotidFemaleHumansIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsMaleMiceMice, Knockout, ApoEMiddle AgedPeptide FragmentsReceptors, CXCR4SialyltransferasesSignal TransductionConceptsMacrophage migration inhibitory factorCXC motif chemokine receptor 4Chemokine receptorsChemokine/receptor axisCXCR4/CXCL12 interactionHuman carotid endarterectomy specimensMigration inhibitory factorChemokine receptor 4MIF/CD74Carotid endarterectomy specimensAtherogenic inflammationCXCL12 interactionReceptor axisReceptor 4MIF inhibitorsReceptor-based strategiesAtherosclerotic plaquesAtherosclerosisAtypical chemokineLeukocyte adhesionCell activityProtective pathwaysInflammationChemokinesPlaques