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 Articles by WOODS, D. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by CANTIN, A. M.
Right arrow Articles by WOODS, D. E.

Am. J. Respir. Crit. Care Med., Volume 160, Number 4, October 1999, 1130-1135

Aerosolized Prolastin Suppresses Bacterial Proliferation in a Model of Chronic Pseudomonas aeruginosa Lung Infection

ANDRÉ M. CANTIN and DONALD E. WOODS

Unité de Recherche Pulmonaire, Université de Sherbrooke, Sherbrooke, Quebec; and Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada

High levels of active neutrophil elastase (HNE) are present in the respiratory secretions of patients with cystic fibrosis (CF). We hypothesized that aerosolized Prolastin (alpha1-protease inhibitor or alpha 1PI, purified from human blood) could suppress airway neutrophil inflammation and accelerate bacterial clearance from the lung in a model of chronic Pseudomonas aeruginosa lung infection. Because human alpha 1PI effectively inhibits rat as well as human neutrophil elastase (NE) activity in vitro, we choose to test this hypothesis using a rat agar bead model of chronic P. aeruginosa lung infection. In this model, aerosolized Prolastin significantly decreased elastase activity (p < 0.01), lung neutrophil counts (p < 0.01), and bacterial colony counts (p < 0.01). Prolastin had no direct bactericidal effect on P. aeruginosa in vitro. Lung tissue histopathology revealed a marked decrease in lung inflammation in animals treated with Prolastin. These studies indicate that Prolastin can significantly decrease the elastase burden in the chronically infected lung. In addition, not only does Prolastin suppress lung inflammation, but it also markedly decreases P. aeruginosa density in a rat model of chronic P. aeruginosa lung infection. These data suggest that aerosolized alpha 1PI may represent a useful nonantibiotic adjunct in the treatment and control of infection and inflammation associated with CF lung disease.




This article has been cited by other articles:


Home page
 Lab AnimHome page
I Kukavica-Ibrulj and R C Levesque
Animal models of chronic lung infection with Pseudomonas aeruginosa: useful tools for cystic fibrosis studies
Lab Anim, October 1, 2008; 42(4): 389 - 412.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
E. D. Chan and M. D. Iseman
Significance of Bronchiectasis in Patients with {alpha}1-Antitrypsin Deficiency
Am. J. Respir. Crit. Care Med., July 15, 2008; 178(2): 208 - 208.
[Full Text] [PDF]

Home page
 J Antimicrob ChemotherHome page
P. Meers, M. Neville, V. Malinin, A. W. Scotto, G. Sardaryan, R. Kurumunda, C. Mackinson, G. James, S. Fisher, and W. R. Perkins
Biofilm penetration, triggered release and in vivo activity of inhaled liposomal amikacin in chronic Pseudomonas aeruginosa lung infections
J. Antimicrob. Chemother., April 1, 2008; 61(4): 859 - 868.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
A. Bellemare, N. Vernoux, D. Morisset, and Y. Bourbonnais
Human Pre-Elafin Inhibits a Pseudomonas aeruginosa-Secreted Peptidase and Prevents Its Proliferation in Complex Media
Antimicrob. Agents Chemother., February 1, 2008; 52(2): 483 - 490.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
M. Griese, P. Latzin, M. Kappler, K. Weckerle, T. Heinzlmaier, T. Bernhardt, and D. Hartl
{alpha}1-Antitrypsin inhalation reduces airway inflammation in cystic fibrosis patients
Eur. Respir. J., February 1, 2007; 29(2): 240 - 250.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
C. Kooi, C. R. Corbett, and P. A. Sokol
Functional Analysis of the Burkholderia cenocepacia ZmpA Metalloprotease
J. Bacteriol., July 1, 2005; 187(13): 4421 - 4429.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
A. Brown, K. Farmer, L. MacDonald, N. Kalsheker, D. Pritchard, C. Haslett, J. Lamb, and J.-M. Sallenave
House Dust Mite Der p 1 Downregulates Defenses of the Lung by Inactivating Elastase Inhibitors
Am. J. Respir. Cell Mol. Biol., September 1, 2003; 29(3): 381 - 389.
[Abstract] [Full Text] [PDF]

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
 ChestHome page
J. G. W. Burdon, S. Brenton, M. Ayad, K. Knight, and J. Lieberman
Augmentation Therapy in {alpha}1-Antitrypsin Deficiency
Chest, August 1, 2001; 120(2): 687 - 687.
[Full Text] [PDF]

Home page
 J. Immunol.Home page
H. T. Akinbi, R. Epaud, H. Bhatt, and T. E. Weaver
Bacterial Killing Is Enhanced by Expression of Lysozyme in the Lungs of Transgenic Mice
J. Immunol., November 15, 2000; 165(10): 5760 - 5766.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
J. Lieberman
Augmentation Therapy Reduces Frequency of Lung Infections in Antitrypsin Deficiency : A New Hypothesis With Supporting Data
Chest, November 1, 2000; 118(5): 1480 - 1485.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 1999 American Thoracic Society 		  Work-Life