Early alterations in airway mucociliary clearance and inflammation
of the lamina propria in cf mice.
Zahm, Jean-Marie, Dominique Gaillard, Florence Dupuit, Jocelyne
Hinnrasky, David Porteous, Julia R. Dorin, Edith Puchelle.
INSERM U314, IFR53, CHU Maison Blanche, Reims, France, MRC Human
Genetics Unit, Western General Hospital, Edinburgh, U.K.
APStracts 3:0374C, 1996.
In cystic fibrosis (CF), whether CFTR dysfunction leads to decreased
mucociliary clearance and mucus hypersecretion, before bacterial
infection, remains an open question. In order 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 cftrm1HGU/cftrm1HGU transgenic mice (Dorin
et al., Nature, 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 cftrm1HGU mutant mice as compared
to the control mice (nasal PD: -7.1+/-0.6 mV and -4.6+/-0.5mV
respectively, p<0.01; tracheal PD: -30.8+/-2.1 mV and -21.4+/-1.8
mV, respectively, p<0.04). In the cftrm1HGU/cftrm1HGU mice, the
mucociliary transport velocity was significantly lower (14.2+/-4.4
[mu]m/mn,- p<0.04), compared to the control mice (30.6+/-5.9
[mu]m/mn). The number of inflammatory cells in the lamina propria was
significantly higher in the cftrm1HGU/cftrm1HGU mice (1048.7+/-124.7
cells/mm2, p<0.03) compared to 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, prior to any airway infection.
Received 26 March 1996; accepted in final form 21 October 1996.
APS Manuscript Number C171-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996