Aline Andrea da Cunha1, Nailê Karine Nuñez1, Rodrigo Godinho de Souza1, Mauro Henrique Moraes Vargas1, Josiane Silva Silveira1, Géssica Luana Antunes1, Laíse da Silva Durante1, Bárbara Nery Porto2, Elisa Simon Marczak3, Marcus Herbert Jones4, Paulo Márcio Pitrez1. 1. a Laboratory of Pediatric Respirology, Infant Center, Institute of Biomedical Research , Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre , Brazil. 2. b Laboratory of Clinical and Experimental Immunology, Infant Center, Institute of Biomedical Research , Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre , Brazil. 3. c Laboratory of Cellular and Molecular Immunology, Institute of Biomedical Research , Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre , Brazil. 4. d Laboratory of Respiratory Physiology, Infant Center, Institute of Biomedical Research , Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre , Brazil.
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.
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.
Entities:
Keywords:
DNA extracellular trap; asthma; inflammation; lung function; rhDNase
Authors: Hanan M El-Laithy; Amal Youssef; Shereen S El-Husseney; Nesrine S El Sayed; Ahmed Maher Journal: Drug Deliv Date: 2021-12 Impact factor: 6.419