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A method for measuring mouse respiratory allergic reaction to low-dose chemical exposure to allergens: an environmental chemical of uncertain allergenicity, a typical contact allergen and a non-sensitizing irritant.

Abstract
Our aim was to improve a method for detecting respiratory hypersensitivity by testing three confirmed respiratory allergens (trimellitic anhydride [TMA], phthalic anhydride [PA] and toluene diisocyanate [TDI]), an environmental chemical of uncertain allergenicity (2,4-d-butyl [DB]), a confirmed contact allergen (2,4-dinitrochlorobenzene [DNCB]) and a standard irritant (sodium dodecyl sulfate [SDS]). BALB/c mice were topically sensitized (nine times in 3 weeks) with these chemicals, then challenged via the trachea. One day post-challenge, samples were taken from the mice to assay for total immunoglobulin (IgE and IgG(1)) levels in serum and bronchoalveolar lavage fluid (BALF); differential cell counts and cytokine/chemokine levels in BALF; lymphocyte counts and surface antigen expression on B-cells within lung-associated lymph nodes (LNs); ex situ cytokine production by cells from these LNs; and gene expression in BALF (CCR3) and LNs (CCR4, STAT6 and GATA-3). The three confirmed respiratory allergens and DB induced immune response characteristic of immediate-type respiratory reactions, as evidenced by increased total IgE and IgG(1) levels; influx of eosinophils, neutrophils, chemokines and cytokines in BALF; increased surface antigen expression on B-cells in LNs; increased Th2 cytokine production in LNs; and increased respiratory allergy-related gene expression in both BALF and LNs. In contrast, DNCB and SDS treatments yielded, at most, insignificant increases in all respiratory allergic parameters. Thus, the protocol was equally suitable for use with an environmental chemical of unknown allergenicity and for typical respiratory allergens. Since the protocol differentiated respiratory allergens from contact allergens and irritants, it may be useful for detecting respiratory allergy related to environmental chemicals.
AuthorsTomoki Fukuyama, Yukari Tajima, Hideo Ueda, Koichi Hayashi, Yasufumi Shutoh, Takanori Harada, Tadashi Kosaka
JournalToxicology letters (Toxicol Lett) Vol. 195 Issue 1 Pg. 35-43 (May 19 2010) ISSN: 1879-3169 [Electronic] Netherlands
PMID20219652 (Publication Type: Journal Article)
CopyrightCopyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.
Chemical References
  • Allergens
  • Cytokines
  • Dinitrochlorobenzene
  • Immunoglobulin G
  • Irritants
  • Sodium Dodecyl Sulfate
  • Immunoglobulin E
Topics
  • Allergens (administration & dosage, toxicity)
  • Animals
  • Bronchoalveolar Lavage Fluid (chemistry, cytology)
  • Cytokines (analysis, metabolism)
  • Dinitrochlorobenzene (toxicity)
  • Drug Administration Routes
  • Female
  • Flow Cytometry
  • Immunoglobulin E
  • Immunoglobulin G
  • Irritants (toxicity)
  • Mice
  • Mice, Inbred BALB C
  • Respiratory Hypersensitivity (chemically induced)
  • Sodium Dodecyl Sulfate (toxicity)

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