title: Recombinant human deoxyribonuclease therapy improves airway resistance and reduces DNA extracellular traps in a murine acute asthma model.
abstract: OBJECTIVE
  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.
authors.affiliation: a Laboratory of Pediatric Respirology, Infant Center, Institute of Biomedical Research , Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre , Brazil.
authors.forename: Aline Andrea
authors.initials: AA
authors.lastname: da Cunha
authors.affiliation: a Laboratory of Pediatric Respirology, Infant Center, Institute of Biomedical Research , Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre , Brazil.
authors.forename: Nailê Karine
authors.initials: NK
authors.lastname: Nuñez
authors.affiliation: a Laboratory of Pediatric Respirology, Infant Center, Institute of Biomedical Research , Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre , Brazil.
authors.forename: Rodrigo Godinho
authors.initials: RG
authors.lastname: de Souza
authors.affiliation: a Laboratory of Pediatric Respirology, Infant Center, Institute of Biomedical Research , Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre , Brazil.
authors.forename: Mauro Henrique
authors.initials: MH
authors.lastname: Moraes Vargas
authors.affiliation: a Laboratory of Pediatric Respirology, Infant Center, Institute of Biomedical Research , Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre , Brazil.
authors.forename: Josiane Silva
authors.initials: JS
authors.lastname: Silveira
authors.affiliation: a Laboratory of Pediatric Respirology, Infant Center, Institute of Biomedical Research , Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre , Brazil.
authors.forename: Géssica Luana
authors.initials: GL
authors.lastname: Antunes
authors.affiliation: a Laboratory of Pediatric Respirology, Infant Center, Institute of Biomedical Research , Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre , Brazil.
authors.forename: Laíse da Silva
authors.initials: Lda S
authors.lastname: Durante
authors.affiliation: b Laboratory of Clinical and Experimental Immunology, Infant Center, Institute of Biomedical Research , Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre , Brazil.
authors.forename: Bárbara Nery
authors.initials: BN
authors.lastname: Porto
authors.affiliation: c Laboratory of Cellular and Molecular Immunology, Institute of Biomedical Research , Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre , Brazil.
authors.forename: Elisa Simon
authors.initials: ES
authors.lastname: Marczak
authors.affiliation: d Laboratory of Respiratory Physiology, Infant Center, Institute of Biomedical Research , Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre , Brazil.
authors.forename: Marcus Herbert
authors.initials: MH
authors.lastname: Jones
authors.affiliation: a Laboratory of Pediatric Respirology, Infant Center, Institute of Biomedical Research , Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre , Brazil.
authors.forename: Paulo Márcio
authors.initials: PM
authors.lastname: Pitrez
mesh_terms: D000281:Administration, Intranasal / Q000379:methods; D000402:Airway Obstruction / Q000188:drug therapy / Q000378:metabolism; D000403:Airway Resistance / Q000187:drug effects*; D000485:Allergens / Q000494:pharmacology; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000188:drug therapy / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid; D004247:DNA / Q000378:metabolism*; D003851:Deoxyribonucleases / Q000494:pharmacology*; D004195:Disease Models, Animal; D065206:Extracellular Traps / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009093:Mucus / Q000187:drug effects / Q000378:metabolism; D010047:Ovalbumin / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology*
chemical_list: D000485:Allergens; D011994:Recombinant Proteins; D010047:Ovalbumin; D004247:DNA; D003851:Deoxyribonucleases
keywords: DNA extracellular trap; asthma; inflammation; lung function; rhDNase