LUNG SURFACTANT IN A CYSTIC-FIBROSIS ANIMAL-MODEL - INCREASED ALVEOLAR PHOSPHOLIPID POOL SIZE WITHOUT ALTERED COMPOSITION AND SURFACE-TENSION FUNCTION IN CFTR(M1HGU M1HGU) MICE/

Background - Progressive pulmonary dysfunction is a characteristic sym ptom of cystic fibrosis (CF) and is associated with functional impairm ent and biochemical alterations of surfactant phospholipids in the air ways. However, the fundamental question of whether surfactant alterati ons in the CF lung are secondary to the pulmonary damage or are presen t before initiation of chronic infection and inflammation has yet to b e resolved in patients with cystic fibrosis but can now be addressed i n CF mice that exhibit the basic defect in the airways. A study was th erefore undertaken to investigate the pool sizes, composition, and fun ction of lung surfactant in the non-infected cftr(mlHGU/mlHGU) mouse. Methods - The amount and composition of phospholipid classes and phosp hatidylcholine molecular species were determined in bronchoalveolar la vage (BAL) fluid and lavaged lungs by high performance liquid chromato graphy (HPLC). Surfactant protein A (SP-A) levels in BAL fluid were de termined by ELISA and surfactant for functional measurements was isola ted from BAL fluid by differential ultracentrifugation. Equilibrium an d minimal surface tension of surfactant was assessed by the pulsating bubble surfactometer technique. MF1, BALB/c, C57/BL6, and C3H/He mice served as controls. Results - BAL fluid of cftr(mlHGU/mlHGU) mice cont ained 1.02 (95% confidence interval (CI) 0.89 to 1.16) mu mol phosphol ipid and 259 (239 to 279) ng SP-A. BAL fluid of MF1, BALB/c, C57BL/6, and C3H/He mice contained 0.69 (0.63 to 0.75), 0.50 (0.42 to 0.57), 0. 52 (0.40 to 0.64), and 0.45 (0.27 to 0.63)pmol phospholipid, respectiv ely. After correction for the different body weights of mouse strains, phospholipid levels in BAL fluid of cftr(mlHGU/mlHGU) mice were incre ased by 64 (52 to 76)%, 60 (39 to 89)%, 72 (45 to 113)%, and 92 (49 to 163)%, respectively, compared with controls. The amount of SP-A in BA L fluid and the composition of phospholipid as well as phosphatidylcho line molecular species in BAL fluid and lung tissue was unchanged in c ftr(mlHGU/mlHGU) mice compared with controls. The increase in phosphol ipids in BAL fluid of cftr(mlHGU/mlHGU) mice resulted from an increase d fraction of large aggregates which exhibited normal surface tension function. Conclusion - In cftr(mlHGU/mlHGU) mice surfactant homeostasi s is perturbed by an increased phospholipid pool in the alveolar compa rtment.