Journal article
A Novel Host Defense System of Airways Is Defective in Cystic Fibrosis
American journal of respiratory and critical care medicine, Vol.175(2), pp.174-183
01/15/2007
DOI: 10.1164/rccm.200607-1029OC
PMCID: PMC2720149
PMID: 17082494
Abstract
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 H
2
O
2
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.
Details
- Title: Subtitle
- A Novel Host Defense System of Airways Is Defective in Cystic Fibrosis
- Creators
- Patryk Moskwa - 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, FranceDaniel Lorentzen - 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, FranceKatherine J. D. A Excoffon - 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, FranceJoseph Zabner - 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, FrancePaul B McCray - 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, FranceWilliam M Nauseef - 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, FranceCorinne Dupuy - 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, FranceBotond 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
- Resource Type
- Journal article
- Publication Details
- American journal of respiratory and critical care medicine, Vol.175(2), pp.174-183
- DOI
- 10.1164/rccm.200607-1029OC
- PMID
- 17082494
- PMCID
- PMC2720149
- NLM abbreviation
- Am J Respir Crit Care Med
- ISSN
- 1073-449X
- eISSN
- 1535-4970
- Publisher
- American Thoracic Society
- Language
- English
- Date published
- 01/15/2007
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Microbiology and Immunology; Pulmonary Medicine; Anatomy and Cell Biology; Infectious Diseases; Stead Family Department of Pediatrics; Otolaryngology; Internal Medicine
- Record Identifier
- 9984093373502771
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