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Development and characterization of an immune mouse model for toluene diisocyanate asthma.

Authors
Matheson-JM; Luster-MI
Source
FASEB J 2003 Apr; 17(7):C249
NIOSHTIC No.
20023202
Abstract
Isocyanate-induced asthma, which is the most common type of occupational asthma, has been difficult to diagnose and control, in part, because the biological mechanisms responsible for the disease and the determinants of exposure have not been well defined. To address these issues, a murine model was established and characterized that reflects exposure conditions that occur in the workplace. C57BL/6J mice were sensitized to toluene diisocyanate (TDI) by inhalation for 6 weeks (20ppb, 4hrs/day, 5 days/week) and challenged 14 days later by inhalation with TDI (20ppb, 1hr). Mice demonstrated allergic asthma evidenced by marked increases in airway inflammation, lung eosinophilia, goblet cell metaplasia, epithelial cell thickening, airway hyper-reactivity, Th2 cytokine expression, and serum IgE levels as well as TDI-specific IgG antibodies. Adoptive transfer with T and B lymphocytes from sensitized mice indicated that both cellular and humoral immunity played a role in the asthma response. Additional studies involving passive transfer and the use of transgenic FcErIg knockout mice, which lack IgE and IgG Fc receptors, established the importance of reagenic antibodies. Taken together, these results suggest that in subchronic model, with a dose reflective of the current permissible workplace exposure level, that sensitization to TDI can occur under these conditions and demonstrates the importance of both a cellular and humoral response in the manifestation of TDI-induced asthma.
Keywords
Respiratory-system-disorders; Pulmonary-system-disorders; Toluenes; Animal-studies; Laboratory-animals; Cellular-reactions; Isocyanates; Bronchial-asthma
CODEN
FAJOEC
CAS No.
584-84-9
Publication Date
20030414
Document Type
Abstract; Conference/Symposia Proceedings
Fiscal Year
2003
NTIS Accession No.
NTIS Price
Issue of Publication
7
ISSN
0892-6638
NIOSH Division
HELD
Source Name
The FASEB Journal, Immunology 2003, Denver, Colorado May 6-10, 2003
State
WV
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