Dermal exposure determines the outcome of repeated airway exposure in a long-term chemical-induced asthma-like mouse model.
Toxicology
; 421: 84-92, 2019 06 01.
Article
em En
| MEDLINE
| ID: mdl-31071364
ABSTRACT
BACKGROUND:
Exposure to diisocyanates is an important cause of occupational asthma (OA) in the industrialized world. Since OA occurs after long-term exposure to diisocyanates, we developed a chronic mouse model of chemical-induced asthma where toluene diisocyanate (TDI) was administered at two different exposure sites.OBJECTIVES:
Evaluating the effect of long-term respiratory isocyanate exposure - with or without prior dermal exposure- on sensitization, inflammatory responses and airway hyperreactivity (AHR).METHODS:
On days 1 and 8, BALB/c mice were dermally treated (20 µl/ear) with 0.5% 2,4-toluene diisocyanate TDI or the vehicle acetone olive oil (AOO) (32). Starting from day 15, mice received intranasal instillations with 0.1% TDI of vehicle five times in a week, for five successive weeks. One day after the last instillation airway hyperreactivity (AHR) to methacholine was assessed, followed by an evaluation of pulmonary inflammation and structural lung changes. Immune-related parameters were assessed in the lungs (BAL and tissue), blood, cervical- and auricular lymph nodes.RESULTS:
Mice repeatedly intranasally exposed to TDI showed systemic sensitization and a mixed Th1/Th2 type immune response, without the presence of AHR. However, when mice are first dermally sensitized with TDI, followed by repeated intranasal TDI challenges, this results in a pronounced Th2 response and AHR.CONCLUSION:
Dermal exposure to TDI determines airway hyperreactivity after repeated airway exposure to TDI.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Asma
/
Tolueno 2,4-Di-Isocianato
/
Modelos Animais de Doenças
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article