Development and Characterization of an Immune Mouse Model for Toluene Diisocyanate Asthma

Details

• Personal Author:
  Luster MI ; Matheson JM
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Animals Asthma Asthma, Occupational Isocyanates Laboratories Occupational Health Respiratory Tract Diseases Safety Toluene
• Keywords:
  Animal-studies Bronchial-asthma Cellular-reactions Laboratory-animals Pulmonary-system-disorders Respiratory-system-disorders Toluenes
• ISSN:
  0892-6638
• Document Type:
  Text
• Genre:
  Abstract or Summary ; Proceedings
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  17
• Issue:
  7
• NIOSHTIC Number:
  nn:20023202
• Citation:
  FASEB J 2003 Apr; 17(7):C249
• CAS Registry Number:
  Toluene 2,4-diisocyanate (CAS RN 584-84-9)
• Federal Fiscal Year:
  2003
• Peer Reviewed:
  False
• Source Full Name:
  The FASEB Journal, Immunology 2003, Denver, Colorado May 6-10, 2003
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:46da9f9a415aa492dce1a14d47a1713f78b17c8eb3985e1c2d7b12da04058d80369d321321068e389db62a60c74b458fd94701cd8aa0aff484eec16e56245900
• Download URL:
  https://stacks.cdc.gov/view/cdc/195756/cdc_195756_DS1.pdf
• File Type:
  [PDF - 524.25 KB ]