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PMID: 2251263 Published · ppublish English Journal Article

Recombinant human DNase I reduces the viscosity of cystic fibrosis sputum.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 87 ·No. 23 ·1990-12-00 ·Pages 9188-92

Shak S, Capon DJ, Hellmiss R, Marsters SA, Baker CL

Abstract

Respiratory distress and progressive lung destruction in cystic fibrosis can be attributed to bacterial persistence and the accumulation of viscous purulent secretions in the airways. More than 30 yr ago it was suggested that the large amounts of DNA in purulent secretions contribute to its viscosity and that bovine pancreatic DNase I could reduce the viscosity. To evaluate the potential clinical utility of recombinant human DNase I (rhDNase) in the treatment of cystic fibrosis, we have cloned, sequenced, and expressed rhDNase. Catalytic amounts of rhDNase greatly reduce the viscosity of purulent cystic fibrosis sputum, transforming it within minutes from a nonflowing viscous gel to a flowing liquid. The reduction in viscosity is associated with a decrease in size of DNA in the sputum. Inhalation of a rhDNase aerosol may be a simple direct approach that will help individuals with cystic fibrosis and other patients with pneumonia or bronchitis to clear their airways of purulent secretions.

MeSH Terms
Amino Acid Sequence Base Sequence Cloning, Molecular Cystic Fibrosis/physiopathology Deoxyribonuclease I/genetics,pharmacology Gene Library Humans Models, Molecular Molecular Sequence Data Oligonucleotide Probes Pancreas/enzymology Protein Conformation Recombinant Proteins/pharmacology Sequence Homology, Nucleic Acid Sputum/drug effects,physiology
Chemicals
Oligonucleotide Probes Recombinant Proteins Deoxyribonuclease I
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Shak S
Department of Immunobiology, Genentech, South San Francisco, CA 94080.
Capon D J
Hellmiss R
Marsters S A
Baker C L
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.87.23.9188
Published
1990-12-00
Pages
9188-92
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC55129
Subset
IM
Databases
GENBANK
M55983
External Links
PubMed source DOI: 10.1073/pnas.87.23.9188 PMC Full Text View journal details
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