Disposition of toluene diisocyanate (TDI) following dermal exposure.
Beezhold-DH; Nayak-A; Anderson-S; Green-B; Siegel-P
J Allergy Clin Immunol 2013 Feb; 131(2)(Suppl):AB14
RATIONALE: Diisocyanates are highly potent allergens that cause work-related asthma and allergic disease. We describe a model for dermal exposure to diisocyantates using toluene diisocyanate (TDI) as a prototypic hapten that covalently modifies proteins to characterize the dermal exposure route. METHODS: Ears of BALB/c mice were dosed a single time with TDI (0.1%, 4% and 15%) in acetone. Vehicle exposed mice served as controls. Ears and draining lymph nodes were collected at various time points between 1 hour and 15 days post-exposure and were processed for histology and immunochemical assessment. Monoclonal anti-TDI-haptenated protein (TDI-hp, mAb) and anti-langerin (CD207+) were used to examine antigen localization and processing using immunohistochemical confocal microscopy. RESULTS: Hematoxylin and eosin stained sections of mouse ears exhibited edema, followed by infiltration of immune cells, epidermal sheading, hyperplasia, and remodeling. At early time points staining for TDI-hp was found localized to the stratum corneum and in hair follicles and sebaceous glands. Immunostaining for TDI-hp was observed between 1 hour to 4 days post exposure, but could no longer be detected at later time points. Immunohistochemistry showed co-localization of CD207+ positive Langerhans cells and TDI-hp in the hair follicles. Co-localization of antigen and dendritic cells was observed in the lymph nodes by 48 hrs. CONCLUSIONS: TDI-hp were located mainly in the stratum corneum but the hair follicles and associated sebaceous glands appeared to be the hapten route of entry with subsequent migration of TDI-hp to the lymph nodes. These studies showthe utility of TDImAb for characterizing dermal and systemic exposures.
Pulmonary-system; Pulmonary-system-disorders; Pulmonary-function; Respiratory-system-disorders; Respiratory-irritants; Allergens; Allergic-disorders; Models; Exposure-levels; Skin-exposure; Toluenes; Proteins; Immunology; Animals; Laboratory-animals
Healthcare and Social Assistance; Services
Journal of Allergy and Clinical Immunology