Early Alterations in Airway Mucociliary Clearance and Inflammation of the Lamina Propria in CF Mice

In cystic fibrosis (CF), whether cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction leads to decreased mucociliary clearance and mucus hypersecretion, before bacterial infection, remains an open question. To answer this question, we quantified in a blind trial the mucociliary transport velocity, the histological state, and the degree of inflammation of the tracheal mucosa in 23 cftr(m1HGU/cftr(m1HGU) transgenic mice (Dorin, J. R., P. Dickinson, E. W. F. W. Alton, S. N. Smith, D. M. Geddes, B. J. Stevenson, W. L. Kimber, S. Fleming, A. R. Clark, M. L. Hooper, L. Anderson, R. S. P. Beddington, and D. J. Porteous. Nature Lond. 359: 211-215, 1992) and in 30 control littermates housed in pathogen-free conditions. The nasal and tracheal transepithelial potential difference (PD) measured in basal conditions was significantly more negative in the cftr(m1HGU) mutant mice as compared with the control mice (nasal PD: -7.1 +/- 0.6 and -4.6 +/- 0.5 mV, respectively, P < 0.01; tracheal PD: -30.8 +/- 2.1 and -21.4 +/- 1.8 mV, respectively, P < 0.04). In the cftr(m1HGU)/cftr(m1HGU) mice, the mucociliary transport velocity was significantly lower (14.2 +/- 4.4 microm/mm, P < 0.04) compared with the control mice (30.6 +/- 5.9 microm/mm). The number of inflammatory cells in the lamina propria was significantly higher in the cftr(m1HGU)/cftr(m1HGU) mice (1048.7 +/- 124.7 cells/mm2, P < 0.03) compared with the control mice (640.5 +/- 58.2 cells/mm2). These results suggest that in CF, decreased airway mucociliary clearance and airway submucosal inflammation represent early alterations, before any airway infection.