help button home button
AJRCCM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by CANTIN, A. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by CANTIN, A. M.

Am. J. Respir. Crit. Care Med., Volume 157, Number 2, February 1998, 464-469

DNase I Acutely Increases Cystic Fibrosis Sputum Elastase Activity and its Potential to Induce Lung Hemorrhage in Mice

ANDRÉ M. CANTIN

Unité de Recherche Pulmonaire, Centre Universitaire de Santé de l'Estrie, Fluerimont, Quebec, Canada

The potential of DNase I to increase cystic fibrosis sputum elastase activity and lung damage was evaluated. Sputum from CF patients induced little lung hemorrhage when instilled intranasally in C57BL/6 mice. However, sputum treated in vitro by the addition of 1 mg/ml bovine DNase I showed increased neutrophil elastase activity (7.97 ± 1.56 versus 3.91 ± 0.62 µM, p < 0.01) and induced marked lung hemorrhage in mice (bronchoalveolar lavage fluid hemoglobin = 192.8 ± 40.7 versus 44.5 ± 12.0 µg/ml, p < 0.01). These effects were not observed with DNase I alone in phosphate buffer and were suppressed by the human neutrophil elastase inhibitor methoxysuccinyl-alanyl-alanyl-prolyl-valine-chloromethylketone (MeOSAAPV-CMK). In vivo administration of 2.5 mg aerosolized recombinant human DNase I to patients with CF resulted in a 2.2-fold increase of sputum elastase activity within 1 h of treatment. Elastase levels returned to pre-rhDNase therapy levels 24 h after aerosol treatment. Sputum collected 1 h after rhDNase on 4 separate days from two of six patients in which elastase levels were highest, induced lung hemorrhage when instilled intranasally in mice. We conclude that DNase I therapy of patients with cystic fibrosis can acutely increase the elastase activity of sputum and also its potential to induce hemorrhage in the murine lung.




This article has been cited by other articles:


Home page
 Am. J. Respir. Cell Mol. Bio.Home page
A. M. Cantin, D. E. Woods, D. Cloutier, E. K. Dufour, and R. Leduc
Polyethylene Glycol Conjugation at Cys232 Prolongs the Half-Life of {alpha}1 Proteinase Inhibitor
Am. J. Respir. Cell Mol. Biol., December 1, 2002; 27(6): 659 - 665.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
B. PERKS and J. K. SHUTE
DNA and Actin Bind and Inhibit Interleukin-8 Function in Cystic Fibrosis Sputa . In Vitro Effects of Mucolytics
Am. J. Respir. Crit. Care Med., November 1, 2000; 162(5): 1767 - 1772.
[Abstract] [Full Text]

Home page
 ThoraxHome page
C. E Milla
Long term effects of aerosolised rhDNase on pulmonary disease progression in patients with cystic fibrosis
Thorax, December 1, 1998; 53(12): 1014 - 1017.
[Abstract] [Full Text]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 1998 American Thoracic Society 		  ATS State of the Art Course 2008