Mass Spectrometry-Based Analysis of Murine Bronchoalveolar Lavage Fluid Following Respiratory Exposure to 4,4′-Methylene Diphenyl Diisocyanate Aerosol

Details

• Personal Author:
  Hettick JM ; Law, Brandon F. ; Lin C-C ; Siegel, Paul D. ; Wisnewski AV ; Hettick JM ; Law, Brandon F. ; Lin C-C ; Siegel, Paul D. ; Wisnewski AV
• Description:
  Diisocyanates are highly reactive electrophiles utilized in the manufacture of a wide range of polyurethane products, and have been identified as causative agents of occupational allergic respiratory disease. However, in spite of the significant occupational health burden associated with diisocyanate-induced asthma, the mechanism of disease pathogenesis remains largely unknown. To better understand the fate of inhaled diisocyanates, a nose-only aerosol exposure system was constructed and utilized to expose a BALB/c mouse model to aerosol generated from 4,4'-methylene diphenyl diisocyanate (MDI). Tissue and bronchoalveolar lavage samples were evaluated 4 hours and 24 hours post-exposure for evidence of diisocyanate-protein haptenation, and a label-free quantitative proteomics strategy was employed to evaluate relative changes to protein content of the cellular fraction of the lavage fluid. Following MDI aerosol exposure, expression of a number of proteins with immunological or xenobiotic metabolism relevance is increased, including endoplasmin, cytochrome P450 and argininosuccinate synthase. Western blot analysis indicated MDI-conjugated protein in the lavage fluid, which was identified as serum albumin. Tandem mass spectrometry analysis of MDI-albumin revealed MDI conjugation occurs at a dilysine motif at Lys525, as well as at a glutamine-lysine motif at Lys414, in good agreement with previously published in vitro data on diisocyanate-conjugated serum albumin. [Description provided by NIOSH]
• Subjects:
  Aerosols Albumins Asthma Asthma, Occupational Energy Metabolism Hypersensitivity Immune System Isocyanates Laboratories Lung Nose Occupational Health Respiratory System Respiratory Tract Diseases Safety Sense Organs

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• Keywords:
  4,4-Methylene Diphenyl Diisocyanate Aerosol Albumin Allergic-reactions Alveolar Cells Analytical Processes Author Keywords: Mass Spectrometry Bronchial-asthma Cellular-function Cellular-reactions Diisocyanate Diisocyanates Exposure Assessment Gene Expression Immune Reaction Inhalation Laboratory Animals Laboratory Testing Mass Spectrometry Metabolism Nasal Cavity Occupational Asthma Pathogenesis Protein-biochemistry Proteins Proteomics Pulmonary-function Pulmonary-system-disorders Respiratory-system-disorders Xenobiotics

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• ISSN:
  0049-8254
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article ; Journal Article
• Place as Subject:
  Connecticut ; OSHA Region 1 ; OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH) ; National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division ; HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health ; Workplace Safety & Health
• Location:
  North America ; North America
• Volume:
  48
• Issue:
  6
• NIOSHTIC Number:
  nn:20049999
• Citation:
  Xenobiotica 2018 Jun; 48(6):626-636
• Contact Point Address:
  Justin M. Hettick, Ph.D., NIOSH/HELD/ACIB, 1095 Willowdale Road, MS L4020, Morgantown, WV 26505
• Email:
  jhettick@cdc.gov
• CAS Registry Number:
  Diphenylmethane diisocyanate (CAS RN 101-68-8) ; Diphenylmethane diisocyanate (CAS RN 101-68-8)
• Federal Fiscal Year:
  2018
• NORA Priority Area:
  Manufacturing ; Construction ; Manufacturing ; Construction
• Performing Organization:
  Yale University, New Haven, Connecticut
• Peer Reviewed:
  True
• Start Date:
  20160801
• Source Full Name:
  Xenobiotica
• End Date:
  20200731
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:440b5e63f321f8544c8647bdb726bef3d2299b6c3cfe0297910f4345fcc3d94b0abeeb278263571ce338b6803d3719c1e6d2043f0a2412d0bd4007ec678f6876
• Download URL:
  https://stacks.cdc.gov/view/cdc/210560/cdc_210560_DS1.pdf
• File Type:
  [PDF - 1.20 MB ]