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Biological Chemistry

Mechanism Found For Isocyanate-Induced Asthma

Glutathione mediates response to chemical used in polymer production

by Celia Henry Arnaud
February 9, 2015 | APPEARED IN VOLUME 93, ISSUE 6

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Credit: Adam Wisnewski
Lung tissue in mice exposed to glutathione-MDI conjugates has elevated mucus production (red stain) along the airway and inflammatory cells in the air spaces and underlying tissue.
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Credit: Adam Wisnewski
Lung tissue in mice exposed to glutathione-MDI conjugates has elevated mucus production (red stain) along the airway and inflammatory cells in the air spaces and underlying tissue.

Isocyanates, which are used in the production of polymers such as polyurethane, have been recognized as a trigger for occupational asthma since the 1950s. Decades later, the mechanisms by which isocyanates exert their effects remain unclear. Now, Adam V. Wisnewski, Jian Liu, and Christopher M. Colangelo of Yale University School of Medicine report that the allergic reactions triggered by methyl­ene diphenyl diisocyanate (MDI) might be mediated by glutathione, a tripeptide antioxidant found at high levels in airway fluid (Chem. Res. Toxicol. 2015, DOI: 10.1021/tx5005002). The researchers administered glutathione-MDI conjugates to mice and found that MDI is transferred to a particular lysine residue in albumin, probably via a transcarbamoylation reaction. The immune proteins released in MDI-induced asthma are characteristic of macrophages, whereas proteins produced in other types of asthma are typical of T cells. The researchers also identified proteins that were produced at lower levels, and others at higher levels, in response to MDI exposure. The protein concentration changes could serve as biomarkers for MDI exposure or MDI-induced asthma.

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