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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Binding, Competitive
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Cathepsin G
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Cathepsins / drug effects
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Cathepsins / metabolism
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Cellulose
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Chromatography, Affinity
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Cystic Fibrosis / drug therapy
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Cystic Fibrosis / enzymology
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DNA / metabolism
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DNA / pharmacology*
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Deoxyribonucleases / metabolism
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Deoxyribonucleases / pharmacology*
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Deoxyribonucleases / therapeutic use
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Elastin / metabolism
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Humans
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Leukocyte Elastase / drug effects
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Leukocyte Elastase / metabolism
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Lung / drug effects
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Lung / enzymology
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Lung / metabolism
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Myeloblastin
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Neutrophils / enzymology*
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Oligonucleotides / metabolism
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Oligonucleotides / pharmacology
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Serine Endopeptidases / drug effects*
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Serine Endopeptidases / metabolism
Substances
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Oligonucleotides
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Cellulose
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DNA
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Elastin
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Deoxyribonucleases
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Cathepsins
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Serine Endopeptidases
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CTSG protein, human
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Cathepsin G
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Leukocyte Elastase
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Myeloblastin