2022
Glutathione reactivity with aliphatic polyisocyanates
Wisnewski AV, Liu J. Glutathione reactivity with aliphatic polyisocyanates. PLOS ONE 2022, 17: e0271471. PMID: 35839242, PMCID: PMC9286259, DOI: 10.1371/journal.pone.0271471.Peer-Reviewed Original ResearchConceptsHexamethylene diisocyanateAliphatic polyisocyanatesReaction productsMS/MSTandem MS/MSReversed-phase LC-MSPositive ion modeMajor reaction productsLiquid chromatography-coupled mass spectrometryCoupled-mass spectrometryPolymeric formulationsIon modeGlutathione reactivityFragmentation patternsGSH reactivityS linkageO groupLC-MSPolyisocyanatesIonsIsocyanate productsDiisocyanateImportant productsReactivityMSSevere asthma and death in a worker using methylene diphenyl diisocyanate MDI asthma death
Wisnewski AV, Cooney R, Hodgson M, Giese K, Liu J, Redlich CA. Severe asthma and death in a worker using methylene diphenyl diisocyanate MDI asthma death. American Journal Of Industrial Medicine 2022, 65: 166-172. PMID: 35028957, PMCID: PMC8846433, DOI: 10.1002/ajim.23323.Peer-Reviewed Case Reports and Technical NotesMeSH KeywordsAsthma, OccupationalHumansImmunoglobulin EImmunoglobulin GIsocyanatesOccupational ExposureConceptsCause of deathMedical recordsDiisocyanate asthmaSevere asthmaSerum IgEParaffin-embedded lung tissue sectionsWorkers' medical recordsSmooth muscle hypertrophyTotal serum IgEHallmark of asthmaSevere asthma attacksBasement membrane thickeningLung tissue sectionsPost-mortem findingsEnzyme-linked immunosorbent assayPotential chemical exposuresInflamed airwaysMucus pluggingOccupational asthmaPulmonary embolismTotal IgEAsthma deathsAsthma attacksLung pathologyAutopsy findings
2020
Analysis of Lung Gene Expression Reveals a Role for Cl- channels in Diisocyanate Induced Airway Eosinophilia in a Mouse Model of Asthma Pathology
Wisnewski AV, Liu J, Redlich CA. Analysis of Lung Gene Expression Reveals a Role for Cl- channels in Diisocyanate Induced Airway Eosinophilia in a Mouse Model of Asthma Pathology. American Journal Of Respiratory Cell And Molecular Biology 2020, 0: 25-35. PMID: 32101465, PMCID: PMC7328250, DOI: 10.1165/rcmb.2019-0400oc.Peer-Reviewed Original ResearchConceptsRespiratory tract exposureAirway eosinophiliaMonocytes/macrophagesMouse modelGene expressionGene transcriptsBiological pathwaysAsthma pathologyUpregulated gene transcriptsIgE-independent mechanismsLung gene expressionLung tissue gene expressionCause of asthmaBALB/cTransgenic B cellsTissue gene expressionExpression changesDiisocyanate asthmaSensitized workersAsthma pathogenesisAirway fluidDeficient miceMRNA microarrayEosinophiliaB cellsMolecular Characterization and Experimental Utility of Monoclonal Antibodies with Specificity for Aliphatic Di- and Polyisocyanates
Wisnewski AV, Liu J. Molecular Characterization and Experimental Utility of Monoclonal Antibodies with Specificity for Aliphatic Di- and Polyisocyanates. Monoclonal Antibodies In Immunodiagnosis And Immunotherapy 2020, 39: 66-73. PMID: 32302507, PMCID: PMC7310211, DOI: 10.1089/mab.2020.0006.Peer-Reviewed Original ResearchConceptsBALB/c miceMonoclonal antibodiesOccupational asthmaC miceSerologic detectionDifferent carrier proteinsNew mAbsEpitope specificityUseful research reagentsDisease preventionImmune recognitionStable hybridomasWestern blotAlbumin adductsMouse skinMAbsSurveillance approachSurveillance effortsAntibodiesMolecular determinantsHybridomasAliphatic diComplementary determining regionsMolecular characterizationResearch reagents
2019
Dilysine-Methylene Diphenyl Diisocyanate (MDI), a Urine Biomarker of MDI Exposure?
Wisnewski AV, Nassar AF, Liu J, Bello D. Dilysine-Methylene Diphenyl Diisocyanate (MDI), a Urine Biomarker of MDI Exposure? Chemical Research In Toxicology 2019, 32: 557-565. PMID: 30724074, PMCID: PMC6465083, DOI: 10.1021/acs.chemrestox.8b00262.Peer-Reviewed Original ResearchConceptsRespiratory tract exposureMDI exposureUrine biomarkersSkin exposureUrine of miceFuture translational investigationsWestern blot studiesUrinary biomarkersRespiratory tractExposure surveillanceTranslational investigationsDisease preventionMDI conjugatesMiceUrineBiomarkersCollision-induced dissociation (CID) fragmentation patternsExposureUnderstanding pathwaysMDIIndustrial hygieneAlbuminMS/MSTractPrevention
2017
Polymerization of hexamethylene diisocyanate in solution and a 260.23 m/z [M+H]+ ion in exposed human cells
Wisnewski AV, Liu J, Redlich CA, Nassar AF. Polymerization of hexamethylene diisocyanate in solution and a 260.23 m/z [M+H]+ ion in exposed human cells. Analytical Biochemistry 2017, 543: 21-29. PMID: 29175138, PMCID: PMC5826792, DOI: 10.1016/j.ab.2017.11.017.Peer-Reviewed Original ResearchConceptsHexamethylene diisocyanateCollision-induced dissociation (CID) fragmentation patternsNucleophilic additionImportant industrial chemicalPrimary aminesFragmentation patternsO groupLC-MS/MSLC-MS/MS analysisLC-MSReaction productsIonsMS analysisFormula CIndustrial chemicalsDiisocyanatePolymerizationPolymersReaction targetWaterSolutionAminesDefinitive characterizationMoleculesDimersMass spectrometry-based analysis of murine bronchoalveolar lavage fluid following respiratory exposure to 4,4'-methylene diphenyl diisocyanate aerosol
Hettick JM, Law BF, Lin CC, Wisnewski AV, Siegel PD. Mass spectrometry-based analysis of murine bronchoalveolar lavage fluid following respiratory exposure to 4,4'-methylene diphenyl diisocyanate aerosol. Xenobiotica 2017, 48: 626-636. PMID: 28629263, PMCID: PMC5864557, DOI: 10.1080/00498254.2017.1344791.Peer-Reviewed Original ResearchConceptsLavage fluidOccupational allergic respiratory diseaseBALB/c mouse modelMurine bronchoalveolar lavage fluidDiisocyanate-induced asthmaBronchoalveolar lavage fluidAllergic respiratory diseasesBronchoalveolar lavage samplesDiphenyl diisocyanate aerosolsLabel-free quantitative proteomic strategyMDI conjugationWestern blot analysisHealth burdenLavage samplesRespiratory diseaseAerosol exposureMouse modelDisease pathogenesisRespiratory exposureCausative agentBlot analysisCytochrome P450Argininosuccinate synthaseQuantitative proteomic strategyCellular fractionsReaction products of hexamethylene diisocyanate vapors with “self” molecules in the airways of rabbits exposed via tracheostomy
Wisnewski AV, Kanyo J, Asher J, Goodrich JA, Barnett G, Patrylak L, Liu J, Redlich CA, Nassar AF. Reaction products of hexamethylene diisocyanate vapors with “self” molecules in the airways of rabbits exposed via tracheostomy. Xenobiotica 2017, 48: 488-497. PMID: 28489470, PMCID: PMC5863241, DOI: 10.1080/00498254.2017.1329569.Peer-Reviewed Original ResearchConceptsCollision-induced dissociation (CID) fragmentation patternsReaction productsLower airwaysChemical reactivityLow molecular weight fractionWeight fractionHigh molecular weight fractionAliphatic diisocyanateMolecular weight fractionFragmentation patternsHexamethylenediisocyanateLC-MSHDI vaporAirways of rabbitsBronchoalveolar lavage fluidRabbit bronchoalveolar lavage fluidMoleculesDiisocyanate vaporsMs. 4Albumin. 5Occupational asthmaReactivityBAL fluidAsthma pathogenesisLavage fluid
2016
The influence of diisocyanate antigen preparation methodology on monoclonal and serum antibody recognition
Hagerman LM, Law BF, Bledsoe TA, Hettick JM, Kashon ML, Lemons AR, Wisnewski AV, Siegel PD. The influence of diisocyanate antigen preparation methodology on monoclonal and serum antibody recognition. Journal Of Occupational And Environmental Hygiene 2016, 13: 829-839. PMID: 27124286, PMCID: PMC5016257, DOI: 10.1080/15459624.2016.1183013.Peer-Reviewed Original ResearchMeSH KeywordsAntigensAsthma, OccupationalEnzyme-Linked Immunosorbent AssayEpitopesIsocyanatesOccupational ExposureConceptsOccupational asthmaDifferent conjugatesPolyclonal antibody responsePanel of antigensSpecific antibody clonesHuman serumMDI conjugationPolyclonal serum antibodiesSpecific IgEAntibody responseSerum antibodiesSerologic detectionStandard antigenMonoclonal antibodiesAntibody clonesAntibodiesAsthmaSignificant differencesAntigenSerumMAbsAntibody recognitionAntigenicityMinimal differencesConjugatesIdentification of novel reaction products of methylene-bis-phenylisocyanate (“MDI”) with oxidized glutathione in aqueous solution and also during incubation of MDI with a murine hepatic S9 fraction
Wisnewski AV, Liu J, Nassar AF. Identification of novel reaction products of methylene-bis-phenylisocyanate (“MDI”) with oxidized glutathione in aqueous solution and also during incubation of MDI with a murine hepatic S9 fraction. Toxicology In Vitro 2016, 36: 97-104. PMID: 27453132, PMCID: PMC5010927, DOI: 10.1016/j.tiv.2016.07.011.Peer-Reviewed Original Research
2015
In vitro cleavage of diisocyanate-glutathione conjugates by human gamma-glutamyl transpeptidase-1
Wisnewski AV, Liu J, Nassar AF. In vitro cleavage of diisocyanate-glutathione conjugates by human gamma-glutamyl transpeptidase-1. Xenobiotica 2015, 46: 726-732. PMID: 26678254, PMCID: PMC4848134, DOI: 10.3109/00498254.2015.1118576.Peer-Reviewed Original ResearchImmunochemical detection of the occupational allergen, methylene diphenyl diisocyanate (MDI), in situ
Wisnewski AV, Liu J. Immunochemical detection of the occupational allergen, methylene diphenyl diisocyanate (MDI), in situ. Journal Of Immunological Methods 2015, 429: 60-65. PMID: 26690039, PMCID: PMC4753098, DOI: 10.1016/j.jim.2015.12.008.Peer-Reviewed Original ResearchConceptsKeyhole limpet hemocyaninFreund's adjuvantDiisocyanate-induced asthmaComplete Freund's adjuvantIncomplete Freund's adjuvantLung tissue sectionsFormalin-fixed paraffinOccupational asthmaLower airwaysBooster injectionOccupational allergensAirway cellsAlveolar macrophagesLimpet hemocyaninAdjuvantHealth effectsTissue distributionTissue samplesTissue sectionsAsthmaDot blot analysisFurther studiesImmunochemical studiesBlot analysisEpithelial regionsGlutathione Reaction Products with a Chemical Allergen, Methylene-diphenyl Diisocyanate, Stimulate Alternative Macrophage Activation and Eosinophilic Airway Inflammation
Wisnewski AV, Liu J, Colangelo CM. Glutathione Reaction Products with a Chemical Allergen, Methylene-diphenyl Diisocyanate, Stimulate Alternative Macrophage Activation and Eosinophilic Airway Inflammation. Chemical Research In Toxicology 2015, 28: 729-737. PMID: 25635619, PMCID: PMC4667722, DOI: 10.1021/tx5005002.Peer-Reviewed Original ResearchConceptsEosinophilic inflammatory responseAlternative macrophage activationInflammatory responseChemical allergensMacrophage activationAirway eosinophil numbersEosinophilic airway inflammationInnate immune responseGreater inflammatory responseAirway levelsMDI conjugationAirway inflammationOccupational asthmaIL-12MDI exposureAsthma pathogenesisEosinophil numbersNaïve miceAirway fluidRespiratory tractImmune responseMucus productionSkin exposureMDI conjugatesVivo evidence
2013
Connecting glutathione with immune responses to occupational methylene diphenyl diisocyanate exposure
Wisnewski AV, Liu J, Redlich CA. Connecting glutathione with immune responses to occupational methylene diphenyl diisocyanate exposure. Chemico-Biological Interactions 2013, 205: 38-45. PMID: 23791970, PMCID: PMC3767171, DOI: 10.1016/j.cbi.2013.06.005.Peer-Reviewed Original ResearchMolecular determinants of humoral immune specificity for the occupational allergen, methylene diphenyl diisocyanate
Wisnewski AV, Liu J. Molecular determinants of humoral immune specificity for the occupational allergen, methylene diphenyl diisocyanate. Molecular Immunology 2013, 54: 233-237. PMID: 23295252, PMCID: PMC3563841, DOI: 10.1016/j.molimm.2012.11.017.Peer-Reviewed Original ResearchConceptsEpitope specificityAutologous serum proteinsLow molecular weight chemicalsOccupational asthmaOccupational allergensMolecular determinantsDisease pathogenesisSecreting clonesCDR3 regionWestern blotGene usageMonoclonal antibodiesMajor causeWeight chemicalsIgG1 mAbGermline gene usageHuman albuminImmune specificityMAbsSerum proteinsELISADiagnostic reagentsUseful diagnostic reagentHybridomasSomatic hypermutation
2012
Hexamethylene diisocyanate (HDI) vapor reactivity with glutathione and subsequent transfer to human albumin
Wisnewski AV, Mhike M, Hettick JM, Liu J, Siegel PD. Hexamethylene diisocyanate (HDI) vapor reactivity with glutathione and subsequent transfer to human albumin. Toxicology In Vitro 2012, 27: 662-671. PMID: 23178851, PMCID: PMC3587365, DOI: 10.1016/j.tiv.2012.11.013.Peer-Reviewed Original ResearchConceptsHDI vaporCommon occupational allergensRespiratory tract exposureHuman albuminLevels of GSHReaction productsGSH concentrationVapor exposureIntra-molecular cyclizationClinical responseOccupational allergensAsthma pathogenesisPolyclonal rabbit serumAirway fluidSerologic assaysLower GSH concentrationsVivo reactivityRabbit serumPotential mechanismsGlutathione reactivityMass spectrometryExposureReactivityGSH solutionKey stepBiomonitoring Hexamethylene Diisocyanate (HDI) Exposure Based on Serum Levels of HDI-Specific IgG
Wisnewski AV, Stowe MH, Nerlinger A, Opare-addo P, Decamp D, Kleinsmith CR, Redlich CA. Biomonitoring Hexamethylene Diisocyanate (HDI) Exposure Based on Serum Levels of HDI-Specific IgG. Annals Of Work Exposures And Health 2012, 56: 901-910. PMID: 22449630, PMCID: PMC3471419, DOI: 10.1093/annhyg/mes024.Peer-Reviewed Original ResearchConceptsPersonal protective equipmentSkin exposureExposure surveillanceSpecific serum immunoglobulin GHexamethylene diisocyanate exposureSerum IgG levelsSerum immunoglobulin GNight shift workEnzyme-linked immunosorbentAdverse health effectsAsthma historyDiisocyanate exposureIgG levelsSerum levelsIgG titersChemical allergensPPE useImmune responseRespirator useIsocyanate exposureExposure biomarkersPractical biomarkersBasic demographicsHigh titersHygiene efforts
2010
Pro/Con debate: is occupational asthma induced by isocyanates an immunoglobulin E‐mediated disease?
Wisnewski AV, Jones M. Pro/Con debate: is occupational asthma induced by isocyanates an immunoglobulin E‐mediated disease? Clinical & Experimental Allergy 2010, 40: 1155-1162. PMID: 20545707, PMCID: PMC3121887, DOI: 10.1111/j.1365-2222.2010.03550.x.Peer-Reviewed Original ResearchConceptsAllergen-specific IgEOccupational asthmaIsocyanate asthmaPro/Con DebateScreening/surveillanceCause of asthmaIgE-mediated diseasesHypersensitive individualsLow molecular weight chemicalsEnvironmental AsthmaAllergic asthmaBronchial hyperreactivityHypersensitivity disordersCommon causeAsthmaPathogenic mechanismsIgEChronic exposureCon debateImportant mediatorDiagnostic testsWeight chemicalsDiseaseHypersensitivityPreventionAntigenic changes in human albumin caused by reactivity with the occupational allergen diphenylmethane diisocyanate
Wisnewski AV, Liu J, Redlich CA. Antigenic changes in human albumin caused by reactivity with the occupational allergen diphenylmethane diisocyanate. Analytical Biochemistry 2010, 400: 251-258. PMID: 20123080, PMCID: PMC3106273, DOI: 10.1016/j.ab.2010.01.037.Peer-Reviewed Original ResearchConceptsHigh-performance liquid chromatographyDiphenylmethane diisocyanateConjugation sitesReaction productsCross-linking agentTandem mass spectrometryPolyurethane productionMass spectrometryMDI-exposed workersCause of asthmaHuman albuminSerum immunoglobulin GLiquid chromatographyReaction specificityDiisocyanateSecond lysineMDI conjugationAirway inflammationAnalytical methodSelf proteinsProteomic methodologiesEpitope specificityAntigenic changesClinical researchConjugates
2008
Human innate immune responses to hexamethylene diisocyanate (HDI) and HDI–albumin conjugates
Wisnewski AV, Liu Q, Liu J, Redlich CA. Human innate immune responses to hexamethylene diisocyanate (HDI) and HDI–albumin conjugates. Clinical & Experimental Allergy 2008, 38: 957-967. PMID: 18498542, PMCID: PMC3131007, DOI: 10.1111/j.1365-2222.2008.02982.x.Peer-Reviewed Original ResearchMeSH KeywordsAdipokinesAdministration, InhalationAlbuminsAntigens, CDBlotting, WesternCells, CulturedChemokine CCL2Chitinase-3-Like Protein 1ChitinasesCyanatesEnzyme-Linked Immunosorbent AssayGene ExpressionGlycoproteinsHumansImmunity, InnateIntramolecular OxidoreductasesIsocyanatesLectinsLeukocytes, MononuclearLysosomesMacrophage Migration-Inhibitory FactorsMicroscopy, FluorescenceOligonucleotide Array Sequence AnalysisPolymerase Chain ReactionPolymorphism, GeneticProteinsRNAConceptsPeripheral blood mononuclear cellsInnate immune responseImmune responsePercentage of PBMCHuman peripheral blood mononuclear cellsFlow cytometrySystemic innate immune responseExposure-dependent decreaseMonocyte/macrophage traffickingHuman innate immune responseProtein expressionSpecific inhalation challengeBlood mononuclear cellsAdaptive immune responsesLow-density lipoproteinPattern recognition receptorsInhalation challengeOccupational asthmaClinical spectrumControl antigenMononuclear cellsHDI exposureSerum concentrationsAdaptive immunityGene/protein expression