Mass spectrometry-based analysis of murine bronchoalveolar lavage fluid following respiratory exposure to 4,4’-methylene diphenyl diisocyanate aerosol

Details

• Alternative Title:
  Xenobiotica
• Personal Author:
  Hettick, Justin M. ; Law, Brandon F. ; Lin, Chen-Chung ; Wisnewski, Adam V. ; Siegel, Paul D.
• Description:
  1. 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. 2. 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 an aerosol generated from 4,4'-methylene diphenyl diisocyanate (MDI). Tissue and bronchoalveolar lavage samples were evaluated 4 and 24 h post-exposure for evidence of diisocyanate-protein haptenation, and a label-free quantitative proteomics strategy was employed to evaluate relative changes to the protein content of the cellular fraction of the lavage fluid. 3. Following MDI aerosol exposure, expression of the 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. 4. 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.
• Subjects:
  Aerosol Aerosols Animals Argininosuccinate Synthase Article Asthma Bronchoalveolar Lavage Cytochrome P-450 Enzyme System Diisocyanate Female Isocyanates Mass Spectrometry Membrane Glycoproteins Mice Mice, Inbred BALB C Proteomics

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• Source:
  Xenobiotica. 48(6):626-636
• Pubmed ID:
  28629263
• Pubmed Central ID:
  PMC5864557
• Document Type:
  Journal Article
• Funding:
  R01 OH010941/OH/NIOSH CDC HHSUnited States/
• Volume:
  48
• Issue:
  6
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:4f7a1e9bc503beca4882c6b9c63719b59bf732c2475d80fa928bce5455fb27f0
• Download URL:
  https://stacks.cdc.gov/view/cdc/52769/cdc_52769_DS1.pdf
• File Type:
  [PDF - 3.36 MB ]