Mucus glycoproteins secreted by respiratory epithelial tissue from cystic fibrosis patients

Abstract

Tracheae, bronchi, nasal epithelial, and nasal polyp tissue slices were incubated in tissue culture with [3H]-glucosamine, and the rate of secretion of labeled mucus glycoproteins was measured. Secretion rates were at least 3- to 6-fold higher for all of the samples from nine patients with cystic fibrosis (CF) who were studied, as compared with values for tissue slices from eight young subjects not affected with this disease. The secreted glycoproteins were further purified into one neutral and three acidic fractions by ion-exchange chromatography on DEAE-cellulose. The glycoproteins secreted by respiratory epithelial tissue from cystic fibrosis subjects contained relatively more of two acidic glycoprotein fractions. Double-label experiments with both [3H]-glucosamine and [35S]-sulfate as mucus glycoprotein precursors further substantiated the shift to more acidic components in the purified mucus glycoproteins and, in addition, suggested a higher level of sulfation of these same two acidic glycoprotein fractions. All four of the labeled glycoprotein fractions secreted by cultured human bronchi cochromatographed with authentic mucus glycoproteins purified from sputum of cystic fibrosis subjects by the same techniques. The differences between mucus glycoproteins from cultured CF airway tissue and mucus glycoproteins from other patients' tissue included relatively increased rates of production, level of sulfation, and greater acidity. Further applications of these in vitro techniques should allow the determination of the enzymatic and biochemical causes of these observed differences in the absence of such potentially confounding variables as concurrent airway infection or of oropharyngeal secretions.