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Molecular characterization of trimellitic anhydride-induced respiratory allergy in Brown Norway rats

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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.
Institution: TNO Kwaliteit van Leven
Source:Toxicologic pathology, 7, 36, 985-998
Identifier: 241243
doi: doi:10.1177/0192623308327410
Keywords: 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


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.