Chemokine Receptor 3 (Ccr3) Plays an Important Role in Allergic Rhinitis Induced by Toluene Diisocyanate

Details

• Personal Author:
  Johnson VJ ; Kashon ML ; Luster MI ; Reynolds JS ; Yucesoy, Berran
• Description:
  Rhinitis often precedes and is a co-existing disease in workers with occupational asthma. Therefore, understanding occupational rhinitis may result in new diagnostic and therapeutic strategies that may help prevent the development of asthma. We previously developed a murine model of toluene diisocyanate (TDI) rhinitis displaying increased expression of IL-4, IL-5, IL-13, IFNGamma, TNFalpha and IL-1Beta as well as extensive eosinophil infiltration into the nasal mucosa. Whole-genome expression analysis demonstrated that genes involved in inflammatory cell recruitment/movement and, specifically, chemotaxis, chemokine activation and chemokine receptor binding were differentially expressed in the nasal mucosa of mice with TDI rhinitis. The chemokine receptor 3 (Ccr3) pathway is important for the recruitment of eosinophils and Th2 lymphocytes to sites of allergic inflammation. We hypothesized that the Ccr3:ligand axis is activated in TDI rhinitis leading to the recruitment of Th2 lymphocytes and eosinophils. Mice were exposed to 50 ppb TDI vapor via inhalation for 12 consecutive weekdays and real-time PCR was used to analyze the expression of chemokine, chemokine receptor and immune genes in the nasal mucosa 24 hours following the final exposure. Expression of Ccr3 and its ligands, Ccl11 (eotaxin I) and Ccl24 (eotaxin II) were upregulated in the nasal mucosa following TDI inhalation. Administration of neutralizing anti-Ccr3 antibodies prior to TDI exposure prevented the upregulation of Ccl11 and Ccl24. In addition, neutralization of Ccr3 markedly reduced TDI-induced changes in IL-4, IL-5, IL-13, TNFAlpha and IL-1Beta expression. These results support the hypothesis that Ccr3 is an important mediator of inflammation in TDI rhinitis. [Description provided by NIOSH]
• Subjects:
  Animals Asthma Asthma, Occupational Laboratories Occupational Health Respiratory Tract Diseases Safety
• Keywords:
  Animal-studies Bronchial-asthma Laboratory-animals Pulmonary-system-disorders Respiratory-system-disorders
• ISSN:
  1073-449X
• Document Type:
  Text
• Genre:
  Abstract or Summary
• 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:
  177
• NIOSHTIC Number:
  nn:20034641
• Citation:
  Am J Respir Crit Care Med 2008 Apr; 177(Meeting Abstracts):A297
• CAS Registry Number:
  Toluene 2,4-diisocyanate (CAS RN 584-84-9)
• Federal Fiscal Year:
  2008
• Peer Reviewed:
  False
• Source Full Name:
  American Journal of Respiratory and Critical Care Medicine
• Supplement:
  Meeting Abstracts
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:d49c4179bbb36c3a862de54ecdbd5cd8111e5990264a184ad7ed863dcfe383bd93833f1c4fb33f293b82f979c7b6121f8adeafd2fc78ef4aa14d0513bf083c61
• Download URL:
  https://stacks.cdc.gov/view/cdc/186778/cdc_186778_DS1.pdf
• File Type:
  [PDF - 446.23 KB ]