Development and characterisation of a novel and rapid lung eosinophil influx model in the rat
| Autor: | Andreas Westhof, Melanie Werner-Klein, Rolf Göggel, Klaus J. Erb |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Pulmonary and Respiratory Medicine
Ketotifen Cyclopropanes Ovalbumin Phosphodiesterase Inhibitors Prednisolone Anti-Inflammatory Agents Aminopyridines Immunoglobulin E Mice Dibenzazepines Rats Inbred BN medicine Eosinophilia Animals Pharmacology (medical) Budesonide Lung Eosinophil cationic protein Mice Inbred BALB C medicine.diagnostic_test biology business.industry Biochemistry (medical) Imidazoles respiratory system Eosinophil Asthma respiratory tract diseases Rats Eosinophils Disease Models Animal Bronchoalveolar lavage medicine.anatomical_structure Immunology Benzamides biology.protein Histamine H1 Antagonists Alum Compounds medicine.symptom business Eosinophil peroxidase Bronchoalveolar Lavage Fluid medicine.drug |
| Zdroj: | Pulmonary pharmacologytherapeutics. 21(4) |
| ISSN: | 1094-5539 |
| Popis: | Eosinophils play a major role in the development and severity of asthma. Robust and rapid preclinical animal models are desirable to profile novel therapeutics inhibiting the influx of eosinophils into the airways. To develop a rapid, airway eosinophil recruitment model in the rat, Brown-Norway (BN) rats were immunised with ovalbumin (OVA)/alum on day 0, 1 and 2 and challenged with OVA aerosol on day 5 and 6. On day 7 bronchoalveolar lavage fluid (BALF) was analysed for eosinophil numbers, eosinophil peroxidase (EPO) activity and cytokines. Lung sections were also examined. The immunised animals showed a strong selective influx of eosinophils into the airways correlating with enhanced EPO activity, Interleukin (IL-4), IL-5 and monocytes chemo attractant protein levels in the BALF in comparison to sham-sensitised rats. In addition the immunised rats developed goblet cell metaplasia in the lung and showed OVA specific IgG1 and IgE levels in the serum but no airway hyperreactivity after metacholine challenge. Airway inflammation was suppressed by applying the steroids Budesonide (intra tracheally) and Prednisolone (per orally), Roflumilast a phosphodiesterase-4 inhibitor, and the H1 receptor antagonists Epinastine and Ketotifen. Montelukast, a Leukotriene receptor antagonist and Chromoglycate, a mast cell stabiliser, had no effect in this model. In summary, in this novel preclinical rat model therapeutics expected to inhibit the development of airway eosinophilia can rapidly be tested. |
| Databáze: | OpenAIRE |
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