Gene complementation of airway epithelium in the cystic fibrosis mouse is necessary and sufficient to correct the pathogen clearance and inflammatory abnormalities

Delvac Oceandy, Brendan J. McMorran, Stephen N. Smith, Rainer Schreiber, Karl Kunzelmann, Eric W F W Alton, David A. Hume, Brandon J. Wainwright*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

47 Citations (Scopus)

Abstract

Increasingly, cystic fibrosis (CF) is regarded as an inflammatory disorder where the response of the lung to Pseudomonas aeruginosa is exaggerated as a consequence of processes mediated by the product of the CF gene, CFTR. Of importance to any gene-replacement strategy for treatment of CF is the identification of the cell type(s) within the lung milieu that need to be corrected and an indication whether this is sufficient to restore a normal inflammatory response and bacterial clearance. We generated G551D CF mice transgenically expressing the human CFTR gene in two tissue compartments previously demonstrated to mediate a CFTR-dependent inflammatory response: lung epithelium and alveolar macrophages. Following chronic pulmonary infection with P. aeruginosa, CF mice with epithelial-expressed but not macrophage-specific CFTR showed an improvement in pathogen clearance and inflammatory markers compared with control CF animals. Additionally, these data indicate the general role for epithelial cell-mediated events in the response of the lung to bacterial pathogens and the importance of CFTR in mediating these processes.

Original languageEnglish
Pages (from-to)1059-1067
Number of pages9
JournalHuman Molecular Genetics
Volume11
Issue number9
Publication statusPublished - 1 May 2002

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