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.