Recombinant human deoxyribonuclease therapy improves airway resistance and reduces DNA extracellular traps in a murine acute asthma model
| Autor: | Marcus Herbert Jones, Laíse da Silva Durante, Paulo Márcio Pitrez, Elisa Simon Marczak, Mauro Henrique Moraes Vargas, Aline Andrea da Cunha, Josiane Silva Silveira, Bárbara N. Porto, Nailê Karine Nuñez, Rodrigo Godinho de Souza, Géssica Luana Antunes |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Ovalbumin Clinical Biochemistry Extracellular Traps Cystic fibrosis Mice 03 medical and health sciences 0302 clinical medicine Airway resistance Animals Humans Medicine Lung Molecular Biology Administration Intranasal Asthma Mice Inbred BALB C Deoxyribonucleases biology business.industry Airway Resistance DNA Allergens respiratory system Airway obstruction medicine.disease Mucus Recombinant Proteins respiratory tract diseases Airway Obstruction Disease Models Animal 030104 developmental biology medicine.anatomical_structure 030228 respiratory system Immunology biology.protein Female Nasal administration Bronchial Hyperreactivity business Bronchoalveolar Lavage Fluid |
| Zdroj: | Experimental Lung Research. 42:66-74 |
| ISSN: | 1521-0499 0190-2148 |
| Popis: | Asthma is a highly prevalent chronic inflammatory lung disease characterized by airway hyperresponsiveness to allergens, airway edema, and increased mucus secretion. Such mucus can be liquefied by recombinant human deoxyribonuclease (rhDNase), in which efficacy of rhDNase has been well documented in patients with cystic fibrosis, but little studied in asthma. In the present study, we investigated whether rhDNase intranasal administration improved inflammation and pulmonary function in an experimental model of asthma.Mice were sensitized by two subcutaneous injections of ovalbumin (OVA), on days 0 and 7, followed by three intranasal challenges with OVA on days 14, 15, and 16. A control group, replacing OVA by DPBS, was included. On days 15 and 16, after 2 hours of OVA challenge, mice received 1 mg/mL of intranasal rhDNase.We showed that rhDNase decreased significantly the airway resistance and reduced EETs formation and globet cells hyperplasia.Our results suggest that extracellular DNA in mucus play a role in lower airways obstruction in OVA asthma protocol and that the treatment with rhDNase improved lung function and DNA extracellular traps, with no direct cellular anti-inflammatory effects. |
| Databáze: | OpenAIRE |
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