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Am J Physiol Lung Cell Mol Physiol 281: L740-L747, 2001;
1040-0605/01 $5.00
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Vol. 281, Issue 3, L740-L747, September 2001

G551D CF mice display an abnormal host response and have impaired clearance of Pseudomonas lung disease

B. J. McMorran, J. S. Palmer, D. P. Lunn, D. Oceandy, E. O. Costelloe, G. R. Thomas, D. A. Hume, and B. J. Wainwright

Institute for Molecular Biosciences, University of Queensland, St. Lucia, Queensland 4072, Australia

Several cystic fibrosis (CF) mouse models demonstrate an increased susceptibility to Pseudomonas aeruginosa lung infection, characterized by excessive inflammation and high rates of mortality. Here we developed a model of chronic P. aeruginosa lung disease in mice homozygous for the murine CF transmembrane conductance regulator G551D mutation that provides an excellent model for CF lung disease. After 3 days of infection with mucoid P. aeruginosa entrapped in agar beads, the G551D animals lost substantially more body weight than non-CF control animals and were less able to control the infection, harboring over 40-fold more bacteria in the lung. The airways of infected G551D animals contained altered concentrations of the inflammatory mediators tumor necrosis factor-alpha , KC/N51, and macrophage inflammatory protein-2 during the first 2 days of infection, suggesting that an ineffective inflammatory response is partly responsible for the clearance defect.

cystic fibrosis; mouse model; lung inflammation; bacterial pulmonary clearance


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