Reaction products of hexamethylene diisocyanate vapors with "self" molecules in the airways of rabbits exposed via tracheostomy

• Published in: Xenobiotica 2018-05, Vol.48 (5), p.488-497
• Main Authors: Wisnewski, Adam V., Kanyo, Jean, Asher, Jennifer, Goodrich, James A., Barnett, Grace, Patrylak, Lyn, Liu, Jian, Redlich, Carrie A., Nassar, Ala F.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Body Fluids - metabolism; Chromatography, Liquid; Exposure; glutathione; hexamethylene diisocyanate; Isocyanates - pharmacology; Lung - drug effects; Male; Mass Spectrometry; Models, Molecular; Molecular Weight; Peptides - chemistry; Rabbits; Tracheostomy; Volatilization
• ISSN: 0049-8254; 1366-5928; 1366-5928
• DOI: 10.1080/00498254.2017.1329569

1. Hexamethylenediisocyanate (HDI) is a widely used aliphatic diisocyanate and a well-recognized cause of occupational asthma. 2. "Self" molecules (peptides/proteins) in the lower airways, susceptible to chemical reactivity with HDI, have been hypothesized to play a role in asthma pathogenesis and/or chemical metabolism, but remain poorly characterized. 3. This study employed unique approaches to identify and characterize "self" targets of HDI reactivity in the lower airways. Anesthetized rabbits free breathed through a tracheostomy tube connected to chambers containing either, O 2 , or O 2 plus ∼200 ppb HDI vapors. Following 60 minutes of exposure, the airways were lavaged and the fluid was analyzed by LC-MS and LC-MS/MS. 4. The low-molecular weight (3 kDa) fraction of exposed rabbit BAL fluid identified HDI modification of specific lysines in uteroglobin (aka clara cell protein) and albumin. 5. In summary, this study utilized a unique approach to chemical vapor exposure in rabbits, to identify HDI reaction products with "self" molecules in the lower airways.