The surface-lining layer of airways in cystic fibrosis mice

Lung disease is the major cause of death in individuals suffering from cystic fibrosis (CF), with abnormal lung-lining fluids occurring already in early infancy. However the precise aetiology of CF lung disease is still poorly understood. We investigated the structural components of the airway surface-lining layer in targeted Cftr/Cftr 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 airfluid interface. The aqueous phase did usually extend less than 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/Cftr than in non-CF mice. Neither the ultrastructure of the surfactant film at the air-liquid interface nor the forms assumed by the osmiophilic structures associated with surfactant turnover in the aqueous layer differed significantly in Cftr/Cftr and non-CF mice. Hence, there were no signs of any ultrastructural abnormalities in the surface-lining layer of young adult Cftr/Cftr mice before infection with CF-related pathogens. Surface-lining layer of airways in cf mice 21/08/03 2 Geiser M, Bastian S final, accepted version LCMP-00128-2003.R