Cystic Fibrosis Transmembrane Conductance Regulator is an Epithelial Cell Receptor for Clearance of Pseudomonas aeruginosa from the Lung

The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride ion channel, but its relationship to the primary clinical manifestation of CF, chronic Pseudomonas aeruginosa pulmonary infection, is unclear. We report that CFTR is a cellular receptor for binding, endocytosing, and cleari...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1997-10, Vol.94 (22), p.12088-12093
Main Authors: Pier, G B, Grout, M, Zaidi, T S
Format: Article
Language:English
Subjects:
Animals
Antibodies
Bacteria
Biological Sciences
Cell lines
Cell membranes
Cells
Cells, Cultured
Cystic fibrosis
Cystic Fibrosis Transmembrane Conductance Regulator - genetics
Cystic Fibrosis Transmembrane Conductance Regulator - metabolism
Endocytosis - drug effects
Epithelial cells
Epithelial Cells - microbiology
Humans
Infections
Ingestion
Internalization
Lung - cytology
Lung Diseases - microbiology
Lungs
Mice
Peptide Fragments - pharmacology
Protein Binding
Pseudomonas Infections - microbiology
Receptors, Cell Surface - genetics
Receptors, Cell Surface - metabolism
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Summary:The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride ion channel, but its relationship to the primary clinical manifestation of CF, chronic Pseudomonas aeruginosa pulmonary infection, is unclear. We report that CFTR is a cellular receptor for binding, endocytosing, and clearing P. aeruginosa from the normal lung. Murine cells expressing recombinant human wild-type CFTR ingested 30-100 times as many P. aeruginosa as cells lacking CFTR or expressing mutant Δ F508 CFTR protein. Purified CFTR inhibited ingestion of P. aeruginosa by human airway epithelial cells. The first extracellular domain of CFTR specifically bound to P. aeruginosa and a synthetic peptide of this region inhibited P. aeruginosa internalization in vivo, leading to increased bacterial lung burdens. CFTR clears P. aeruginosa from the lung, indicating a direct connection between mutations in CFTR and the clinical consequences of CF.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.94.22.12088