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          Institute: MPI für Infektionsbiologie     Collection: Department of Cellular Microbiology     Display Documents

ID: 581591.0, MPI für Infektionsbiologie / Department of Cellular Microbiology
Neutrophil Elastase Enhances Sputum Solubilization in Cystic Fibrosis Patients Receiving DNase Therapy
Authors:Papayannopoulos, Venizelos; Staab, Doris; Zychlinsky, Arturo
Date of Publication (YYYY-MM-DD):2011-12-09
Title of Journal:PLoS ONE
Journal Abbrev.:PLoS One
Issue / Number:12
Sequence Number of Article:e28526
Copyright:© 2011 Papayannopoulos et al.
Review Status:Peer-review
Audience:Experts Only
Abstract / Description:Cystic fibrosis patients suffer from chronic lung infection and inflammation due to the secretion of viscous sputum. Sputum viscosity is caused by extracellular DNA, some of which originates from the release of neutrophil extracellular traps (NETs). During NET formation neutrophil elastase (NE) partially processes histones to decondense chromatin. NE is abundant in CF sputum and is thought to contribute to tissue damage. Exogenous nucleases are a palliative treatment in CF as they promote sputum solubilization. We show that in a process reminiscent of NET formation, NE enhances sputum solubilization by cleaving histones to enhance the access of exogenous nucleases to DNA. In addition, we find that in Cf sputum NE is predominantly bound to DNA, which is known to downregulate its proteolytic activity and may restrict host tissue damage. The beneficial role of NE in CF sputum solubilization may have important implications for the development of CF therapies targeting NE.
External Publication Status:published
Document Type:Article
Communicated by:Beate Löhr
Affiliations:MPI für Infektionsbiologie/Department of Cellular Microbiology
External Affiliations:[Staab, Doris] Charite, Christiane Herzog Cyst Fibrosis Ctr, Clin Pediat Pneumol & Immunol, Berlin, Germany.
Identifiers:ISI:000298365700044 [ID No:1]
ISSN:1932-6203 [ID No:2]
DOI:10.1371/journal.pone.0028526 [ID No:3]
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