Recombinant human deoxyribonuclease therapy improves airway resistance and reduces DNA extracellular traps in a murine acute asthma model

ABSTRACT

Purpose: 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. Methods: 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. Results: We showed that rhDNase decreased significantly the airway resistance and reduced EETs formation and globet cells hyperplasia. Conclusions: 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.

KEYWORDS:

• asthma
• DNA extracellular trap
• inflammation
• lung function
• rhDNase

Acknowledgment

We thank José Carlos Farias Alves Filho for his technical assistance.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.

Funding

This study was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq, Brazil.