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Toluene diisocyanate (TDI)-induced asthma: Inflammatory and immunological responses to TDI, ovalbumin (OVA) and ovalbumin peptide OVA 323-339 in mouse models

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dc.contributor.author Sun, Li-Zhi
dc.date.accessioned 2012-06-28T07:59:32Z
dc.date.available 2012-06-28T07:59:32Z
dc.date.issued 2012-06-07
dc.identifier.isbn 978-82-308-2048-3 (print version)
dc.identifier.uri http://hdl.handle.net/1956/5866
dc.description.abstract Among three major diisocyanates: TDI, methylenediphenyl diisocyanate (MDI) and hexamethylene diisocyanate (HDI), TDI has been regarded as the leading cause of diisocyanate-induced asthma. The principal feature of TDI-induced asthma is the airway inflammation with influx of neutrophils, lymphocytes and eosinophils. This in turn leads to the variable airway hyper-responsiveness. TDI-induced asthma can share many similar features with allergic asthma, such as increased total and specific IgE serum levels, activated CD4+ T cells, eosinophils and mast cells, increased levels of IL-4 and IL-5 and airway remodeling. So far, the pathogenic mechanism of TDI-induced asthma is still far from clear. It has been commonly accepted that TDI sensitization involves binding of TDI to carrier molecules. Specific IgE to diisocyanate has been regarded to be helpful in the diagnosis of occupational asthma. Particularly, increased immunoglobulin IgG1 was suggested to be associated to TDI exposure and the protein-conjugated TDI can be a useful marker for progress of TDI-asthma. In the past decades, the reports on the phenotype of immune response to TDI have been quite controversial. Maestrelli et al. reported that increased levels of Th2 cytokines were detected in the airways and bronchial mucosa of TDI asthmatics. However, some authors such as Lummus et al. observed Th1-like response characterized by an increase in the number of neutrophils and the levels of IFN-y and IL-8. In order to better address those issues, we established a TDI BALB/c mouse model by subcutaneous sensitization and intranasal challenge to investigate the inflammatory and immune responses that occurred in the development of TDI-induced asthma. In this model, the Th2 mode was involved since the TDI mice demonstrated Th2-like immune responses with significantly increased serum total IgE, IL-4 and decreased IFN-y. Airway remodeling was initiated in the early phase of the development of the TDI asthma. However, neutrophildominant pulmonary inflammation in TDI-induced mouse model of asthma suggested a different inflammatory phenotype from the eosinophil-dominant allergic responses induced by high molecular weight chemicals, such as OVA and OVA 323-339. There are several different routes of exposure from which the professional workers finally could develop asthma. The skin might function as one of most possible initiative site for sensitization and later on, the final target tissue, airways became hyper-sensitive and asthma occurred. In this context, the improved mouse model by repeated epicutaneous sensitization and intranasal challenge was established. Similar inflammatory and immune responses were triggered as in the mice by subcutaneous sensitization. Furthermore, followed by exposure to TDI, increased airway hypersensitivity was observed when indicated by Penh with the method of plethysmography. It seems that IgG1 may not be ignored as well as IgE in the development of TDI-induced asthma, at least in mouse model of asthma. en
dc.language.iso eng en
dc.publisher The University of Bergen en
dc.relation.haspart Paper I: Scandinavian Journal of Immunology 65 (2), pages 118–125,(2007) L.-Z. Sun, S. Elsayed, A. M. Bronstad, T. Van Do, A . Irgens, N. P. Aardal & T. B. Aasen, Airway Inflammation and Bronchial Remodelling in Toluene Diisocyanate-exposed BALB/c Mouse Model. The paper is available in BORA: <a href="http://hdl.handle.net/1956/5864" target="blank">http://hdl.handle.net/1956/5864</a> en
dc.relation.haspart Paper II: Scandinavian Journal of Immunology 71(5), pages 329–335, (2010), L.-Z. Sun, S. Elsayed, T. B. Aasen, T. Van Do,, N. P. Aardal, E. Florvaag & K. Vaali, Comparison between Ovalbumin and Ovalbumin Peptide 323-339 Responses in Allergic Mice: Humoral and Cellular Aspects. The paper is available in BORA:<a href="http://hdl.handle.net/1956/5865" target="blank">http://hdl.handle.net/1956/5865</a> en
dc.relation.haspart Paper III: Li-Zhi Suna, Thien Van Dob, Erik Florvaag, Nils P Aardald, Jørn Skavlanda and Kirsi Vaali, Toluene diisocyanate-induced bronchial hyper-reactivity and neutrophilic inflammation deviates from the eosinophil-dominant response to ovalbumin. Full-text not available in BORA. en
dc.rights Copyright the author. All rights reserved. en
dc.title Toluene diisocyanate (TDI)-induced asthma: Inflammatory and immunological responses to TDI, ovalbumin (OVA) and ovalbumin peptide OVA 323-339 in mouse models en
dc.type Doctoral thesis en
dc.subject.nsi VDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Medical immunology: 716 en


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