title: Effect of DNase on the activity of neutrophil elastase, cathepsin G and proteinase 3 in the presence of DNA.
abstract: It has been shown previously that DNA binds and inhibits neutrophil elastase (NE). Here we demonstrate that DNA has a better affinity for neutrophil cathepsin G (cat G) than for NE and is a better inhibitor of cat G than of NE. DNase-generated <0.5 kb DNA fragments inhibit NE and cat G as potently as full length DNA. This rationalises our observation that administration of DNase to cystic fibrosis patients does not enhance the NE and cat G activity of their lung secretions. Neutrophil proteinase 3 is not inhibited by DNA and might thus be the most harmful proteinase in inflammatory lung diseases.
authors.affiliation: Laboratoire d'Enzymologie, INSERM Unité 392, Faculté de Pharmacie, Université Louis Pasteur de Strasbourg, F-67400, Illkirch, France.
authors.forename: J
authors.initials: J
authors.lastname: Duranton
authors.forename: D
authors.initials: D
authors.lastname: Belorgey
authors.forename: J
authors.initials: J
authors.lastname: Carrère
authors.forename: L
authors.initials: L
authors.lastname: Donato
authors.forename: T
authors.initials: T
authors.lastname: Moritz
authors.forename: J G
authors.initials: JG
authors.lastname: Bieth
mesh_terms: D001667:Binding, Competitive; D056649:Cathepsin G; D002403:Cathepsins / Q000187:drug effects / Q000378:metabolism; D002482:Cellulose; D002846:Chromatography, Affinity; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000201:enzymology; D004247:DNA / Q000378:metabolism / Q000494:pharmacology*; D003851:Deoxyribonucleases / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D004549:Elastin / Q000378:metabolism; D006801:Humans; D019272:Leukocyte Elastase / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D053146:Myeloblastin; D009504:Neutrophils / Q000201:enzymology*; D009841:Oligonucleotides / Q000378:metabolism / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000187:drug effects* / Q000378:metabolism
chemical_list: D009841:Oligonucleotides; D002482:Cellulose; D004247:DNA; D004549:Elastin; D003851:Deoxyribonucleases; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D019272:Leukocyte Elastase; D053146:Myeloblastin