Enviornmental and Occupational DisordersA novel mouse model of diisocyanate-induced asthma showing allergic-type inflammation in the lung after inhaled antigen challenge☆,☆☆
Section snippets
Animals and epicutaneous sensitization
BALB/c mice were purchased from The National Cancer Institute (Frederick, Md). BALB/c-Il4tm2Nnt (IL-4-/-) mice were purchased from The Jackson Laboratory (Bar Harbor, Me). BALB/c IL-13-/- mice were provided by A. McKenzie. IFN-γ receptor-deficient (IFN-γR-/-) mice were provided by J. Aguet and backcrossed onto BALB/c. Female mice 9 to 12 weeks of age were used in all experiments. Backs of mice were shaved with electric clippers 1 to 2 days before exposure to HDI (0.01%–10%) diluted in a 4:1
CHS and antibody responses in HDI-sensitized mice
As shown in Fig 1, A , mice exposed to either 0.1% or 1.0% HDI on days 0 and 7 had significant ear-swelling responses after challenge on day 12.
Discussion
In the present study we describe a novel mouse model of diisocyanate-induced asthma. To our knowledge, this is the first such model to demonstrate lung inflammation with characteristics of human asthma, including eosinophilia and mucus hypersecretion. The lung inflammation in our model was present specifically in sensitized animals. Scheerens et al7, 8 have reported increased airway reactivity after intratracheal challenge of toluene diisocyanate-sensitized mice. However, only nonspecific,
Acknowledgements
We thank Ms Heather MacLeod for technical assistance and Dr Robert Homer for his input regarding the histologic appearance of lung inflammatory infiltrates.
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Supported by National Institutes of Health grants R01-HL65209 (K. Bottomly and C. Herrick), P50-HL56389 and K24-ES00355 (C. Redlich), and RO1-HL62622 (A. Wisnewski). C. Herrick was supported by a Dermatology Foundation Clinical Career Development Award.
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Reprint requests: Christina A. Herrick, MD, PhD, Department of Dermatology, Yale University School of Medicine, 333 Cedar St, PO Box 208059, New Haven, CT 06520-8059.