help button home button
AJRCCM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Published ahead of print on November 2, 2006, doi:10.1164/rccm.200607-1029OC
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Online Supplement
Right arrow All Versions of this Article:
200607-1029OCv1
175/2/174    most recent
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 Moskwa, P.
Right arrow Articles by Bánfi, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Moskwa, P.
Right arrow Articles by Bánfi, B.
American Journal of Respiratory and Critical Care Medicine Vol 175. pp. 174-183, (2007)
© 2007 American Thoracic Society
doi: 10.1164/rccm.200607-1029OC

Original Article

A Novel Host Defense System of Airways Is Defective in Cystic Fibrosis

Patryk Moskwa, Daniel Lorentzen, Katherine J. D. A. Excoffon, Joseph Zabner, Paul B. McCray, Jr., William M. Nauseef, Corinne Dupuy and Botond Bánfi

Departments of Anatomy and Cell Biology, Internal Medicine, and Pediatrics, and Inflammation Program, Carver College of Medicine, University of Iowa; Department of Veterans Affairs, Iowa City VA Medical Center, Iowa City, Iowa; and Faculté de Pharmacie, Université Paris 11, Châtenay-Malabry, France

Correspondence and requests for reprints should be addressed to Botond Bánfi, M.D., Ph.D., Inflammation Program, University of Iowa, 2501 Crosspark Road, Coralville, IA 52241. E-mail: botond-banfi{at}uiowa.edu

Rationale: The respiratory tract is constantly exposed to airborne microorganisms. Nevertheless, normal airways remain sterile without recruiting phagocytes. This innate immune activity has been attributed to mucociliary clearance and antimicrobial polypeptides of airway surface liquid. Defective airway immunity characterizes cystic fibrosis (CF), a disease caused by mutations in the CF transmembrane conductance regulator, a chloride channel. The pathophysiology of defective immunity in CF remains to be elucidated.

Objective: We investigated the ability of non-CF and CF airway epithelia to kill bacteria through the generation of reactive oxygen species (ROS).

Methods: ROS production and ROS-mediated bactericidal activity were determined on the apical surfaces of human and rat airway epithelia and on cow tracheal explants.

Measurements and Main Results: Dual oxidase enzyme of airway epithelial cells generated sufficient H2O2 to support production of bactericidal hypothiocyanite (OSCN–) in the presence of airway surface liquid components lactoperoxidase and thiocyanate (SCN–). This OSCN– formation eliminated Staphylococcus aureus and Pseudomonas aeruginosa on airway mucosal surfaces, whereas it was nontoxic to the host. In contrast to normal epithelia, CF epithelia failed to secrete SCN–, thereby rendering the oxidative antimicrobial system inactive.

Conclusions: These data indicate a novel innate defense mechanism of airways that kills bacteria via ROS and suggest a new cellular and molecular basis for defective airway immunity in CF.

Key Words: innate immunity • airway infection • Duox • reactive oxygen species


AT A GLANCE COMMENTARY

Scientific Knowledge on the Subject
Lactoperoxidase and thiocyanate are secreted into the airway surface liquid. When H2O2 is artificially added (pipetted) to harvested airway surface liquid, lactoperoxidase catalyzes the formation of bactericidal hypothiocyanite by oxidizing thiocyanate.

What This Study Adds to the Field
Airway epithelia generate sufficient H2O2 to support hypothiocyanite production and hypothiocyanite-mediated bacterial killing. This oxidative host defense system is defective in the cystic fibrosis airway epithelium due to insufficient thiocyanate secretion.

 



This article has been cited by other articles:


Home page
 J. Immunol.Home page
B. Rada, K. Lekstrom, S. Damian, C. Dupuy, and T. L. Leto
The Pseudomonas Toxin Pyocyanin Inhibits the Dual Oxidase-Based Antimicrobial System as It Imposes Oxidative Stress on Airway Epithelial Cells
J. Immunol., October 1, 2008; 181(7): 4883 - 4893.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
A. Almolki, A. Guenegou, S. Golda, L. Boyer, M. Benallaoua, N. Amara, R. Bachoual, C. Martin, F. Rannou, S. Lanone, et al.
Heme Oxygenase-1 Prevents Airway Mucus Hypersecretion Induced by Cigarette Smoke in Rodents and Humans
Am. J. Pathol., October 1, 2008; 173(4): 981 - 992.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Pacquelet, M. Lehmann, S. Luxen, K. Regazzoni, M. Frausto, D. Noack, and U. G. Knaus
Inhibitory Action of NoxA1 on Dual Oxidase Activity in Airway Cells
J. Biol. Chem., September 5, 2008; 283(36): 24649 - 24658.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
X. Liu and J. F. Engelhardt
The Glandular Stem/Progenitor Cell Niche in Airway Development and Repair
Proceedings of the ATS, August 15, 2008; 5(6): 682 - 688.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
C. S. Rogers, W. M. Abraham, K. A. Brogden, J. F. Engelhardt, J. T. Fisher, P. B. McCray Jr., G. McLennan, D. K. Meyerholz, E. Namati, L. S. Ostedgaard, et al.
The porcine lung as a potential model for cystic fibrosis
Am J Physiol Lung Cell Mol Physiol, August 1, 2008; 295(2): L240 - L263.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
W. M. Nauseef
Biological Roles for the NOX Family NADPH Oxidases
J. Biol. Chem., June 20, 2008; 283(25): 16961 - 16965.
[Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
F. J. Accurso
Update in Cystic Fibrosis 2007
Am. J. Respir. Crit. Care Med., May 15, 2008; 177(10): 1058 - 1061.
[Full Text] [PDF]

Home page
 Eur Respir JHome page
P. Schelstraete, S. Van daele, K. De Boeck, M. Proesmans, P. Lebecque, J. Leclercq-Foucart, A. Malfroot, M. Vaneechoutte, and F. De Baets
Pseudomonas aeruginosa in the home environment of newly infected cystic fibrosis patients
Eur. Respir. J., April 1, 2008; 31(4): 822 - 829.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
J. P. Mizgerd and S. J. Skerrett
Animal models of human pneumonia
Am J Physiol Lung Cell Mol Physiol, March 1, 2008; 294(3): L387 - L398.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
B. Banfi
A Novel Host Defense System of Airways Is Defective in Cystic Fibrosis: Update
Am. J. Respir. Crit. Care Med., May 1, 2007; 175(9): 967 - 967.
[Full Text] [PDF]

Home page
 J. Immunol.Home page
N. Pedemonte, E. Caci, E. Sondo, A. Caputo, K. Rhoden, U. Pfeffer, M. Di Candia, R. Bandettini, R. Ravazzolo, O. Zegarra-Moran, et al.
Thiocyanate Transport in Resting and IL-4-Stimulated Human Bronchial Epithelial Cells: Role of Pendrin and Anion Channels
J. Immunol., April 15, 2007; 178(8): 5144 - 5153.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
P. S. Hiemstra
Antimicrobial peptides in the real world: implications for cystic fibrosis
Eur. Respir. J., April 1, 2007; 29(4): 617 - 618.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 2007 American Thoracic Society 		  ATS Best of the Web