Title
Molecular characterization of trimellitic anhydride-induced respiratory allergy in Brown Norway rats
Author
Kuper, C.F.
Heijne, W.H.
Dansen, M.
Verhoeckx, K.C.
Boorsma, A.
Radonjic, M.
Bruijntjes, J.
Stierum, R.
Muijser, H.
Arts, J.H.
TNO Kwaliteit van Leven
Publication year
2008
Abstract
To contribute to the hazard identification of low molecular weight (LMW) respiratory allergens, respiratory allergy induced by trimellitic anhydride (TMA) was characterized by whole genome analysis of lung tissue and blood proteomics in Brown Norway rats. Dermal sensitization (50% and 25% w/v) with TMA and an inhalation challenge of 15 mg/m(3) TMA-induced apneas, laryngeal inflammation, increased numbers of eosinophils, neutrophils and macrophages in bronchoalveolar lavage (BAL), and increased immunoglobulin E levels in serum and lung tissue. Whole genome analysis of lung, sampled 24 hours after challenge, showed expression changes of not only genes belonging to several Gene Ontology groups with up-regulation of inflammatory-associated genes and those associated with lung remodeling but also genes involved in downsizing these processes. Blood proteomics reflected activation of inflammation-inhibiting pathways. Unsensitized animals challenged with TMA exhibited also an increased number of macrophages in BAL, but gene expression in the above-mentioned gene pathways was unchanged or down-regulated. The authors conclude that parameters for lung remodeling can be a valuable tool in hazard identification of LMW respiratory allergens.
Subject
Biology
Toxicology and Applied Pharmacology
Allergen
Immunoglobulin E
Phthalic anhydride
Toll like receptor
Trimellitic anhydride
Analysis of variance
Animal
Article
Blood
Brown Norway rat
Cluster analysis
DNA microarray
Drug effect
Female
Gene expression profiling
Genetics
Immunohistochemistry
Lung
Lung lavage
Metabolism
Nonparametric test
Pathology
Principal component analysis
Proteomics
Rat
Respiratory tract allergy
Signal transduction
Allergens
Analysis of Variance
Animals
Bronchoalveolar Lavage
Cluster Analysis
Female
Gene Expression Profiling
Immunoglobulin E
Immunohistochemistry
Lung
Oligonucleotide Array Sequence Analysis
Phthalic Anhydrides
Principal Component Analysis
Proteomics
Rats
Rats, Inbred BN
Respiratory Hypersensitivity
Signal Transduction
Statistics, Nonparametric
Toll-Like Receptors
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DOI
https://doi.org/10.1177/0192623308327410
TNO identifier
241243
ISSN
1533-1601
Source
Toxicologic pathology, 36 (7), 985-998
Document type
article