Ion composition and rheology of airway liquid from cystic fibrosis fetal tracheal xenografts

The composition of airway surface liquid (ASL) is partly determined by acti ve ion and water transport through the respiratory epithelium. It is usuall y stated that in cystic fibrosis (CF), CF transmembrane conductance regulat or protein abnormality results in imbalanced ion composition and dehydratio n of ASL, leading to abnormal theologic and transport properties. To explor e the relationship between ion composition, water content, and viscosity of airway liquid (AL), we used a human xenograft model of fetal airways devel oped in severe combined immunodeficiency (SCID) mice. Six non-CF and six CF portions of fetal tracheas were engrafted subcutaneously in the flanks of SCID mice raised in pathogen-free conditions. AL accumulated in the closed cylindric grafts was harvested 9 to 17 wk after implantation. At the time o f AL sampling, all tracheal grafts displayed well-differentiated pseudostra tified surface epithelium and submucosal glands. The viscosity of AL was me asured using a controlled-stress rheometer. The ion composition of AL was q uantified by X-ray microanalysis. No significant difference was observed fo r AL viscosity between non-CF (0.6 +/- 0.5 Pa . s) and CF (0.2 +/- 0.1 Pa . s) samples. In AL from non-CF and CF samples, the ion concentrations were Na: 63.9 +/- 7.6, 79.7 +/- 11.6; Cl: 64.9 +/- 13.2, 82.6 +/- 15.7; Mg: 1.9 +/- 0.3, 2.2 +/- 0.4; S: 4.9 +/- 1.3, 4.8 +/- 0.5; K: 2.4 +/- 0.5, 3.2 +/- 1.6; and Ca: 1.2 +/- 0.3, 2.6 +/- 0.8 mmol/liter, respectively. The ion com position of AL from CF versus non-CF xenografts was not significantly diffe rent. These results suggest that prior to inflammation and infection, the v iscosity and ion composition of the fetal AL do not differ in CF and non-CF .