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Surface-lining layer of airways in cystic fibrosis mice

Institute of Anatomy, University of Bern, CH-3000 Bern 9, Switzerland

Submitted 29 April 2003 ; accepted in final form 20 August 2003

Lung disease is the major cause of death in individuals suffering from cystic fibrosis (CF), with abnormal lung-lining fluids occurring as early as early infancy. However, the precise etiology of CF lung disease is still poorly understood. We investigated the structural components of the airway surface-lining layer in targeted Cftr^tm1HGU/Cftr^tm1HGU mutant mice and non-CF controls. Five lungs per animal group were fixed by intravascular triple perfusion. The ultrastructure of the surface-lining layer of large and small intrapulmonary conducting airways was systematically investigated according to a standard protocol in transmission and scanning electron micrographs. In both animal groups, the surface-lining layer consisted of an aqueous phase and an osmiophilic film of variable thickness at the air-fluid interface. The aqueous phase usually did extend <1 µm beyond the uppermost tips of the epithelial cells in both animal groups. The aqueous phase of the small airways was slightly more electron dense in Cftr^tm1HGU/Cftr^tm1HGU than in non-CF mice. Neither the ultrastructure of the surfactant film at the air-fluid interface nor the forms assumed by the osmiophilic structures associated with surfactant turnover in the aqueous layer differed significantly in Cftr^tm1HGU/Cftr^tm1HGU and non-CF mice. Hence, there were no signs of any ultrastructural abnormalities in the surface-lining layer of young adult Cftr^tm1HGU/Cftr^tm1HGU mice before infection with CF-related pathogens.

lung; mouse; surfactant; ultrastructure

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