title: Neutrophil elastase enhances sputum solubilization in cystic fibrosis patients receiving DNase therapy.
abstract: 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.
authors.affiliation: Department of Cellular Microbiology, Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Venizelos
authors.initials: V
authors.lastname: Papayannopoulos
authors.forename: Doris
authors.initials: D
authors.lastname: Staab
authors.forename: Arturo
authors.initials: A
authors.lastname: Zychlinsky
mesh_terms: D000328:Adult; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000201:enzymology*; D004247:DNA / Q000378:metabolism; D003851:Deoxyribonucleases / Q000627:therapeutic use*; D005110:Extracellular Space / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism*; D008954:Models, Biological; D009504:Neutrophils / Q000201:enzymology; D009195:Peroxidase / Q000378:metabolism; D012995:Solubility; D013183:Sputum / Q000201:enzymology*
chemical_list: D006657:Histones; D004247:DNA; D009195:Peroxidase; D003851:Deoxyribonucleases; D019272:Leukocyte Elastase