CYSTIC-FIBROSIS SPUTUM INDUCES A SECRETORY RESPONSE FROM AIRWAY GLANDSEROUS CELLS THAT CAN BE PREVENTED BY NEUTROPHIL PROTEASE INHIBITORS

High activities of the neutrophil proteases, elastase and cathepsin G, are found in the sputum of patients with cystic fibrosis (CF), Becaus e both proteases have been shown to be potent secretagogues for airway submucosal glands, and because hypersecretion is a characteristic fea ture of CF, the objective of the present study was to examine whether there is secretagogue activity in CF sputum, and to determine the cont ribution of neutrophil proteases to the secretagogue activity. Conflue nt monolayers of cultured bovine tracheal serous cells were pulse-labe lled with (Na2SO4)-S-35, incubated with diluted CF sputum supernatants in the presence or absence of different protease inhibitors, and the subsequent release of the radiolabelled macromolecules was measured. C F sputum potently induced secretion concentration-dependently. Additio n of the selective neutrophil elastase inhibitor ICI 200,355 inhibited the secretory response to CP sputum supernatant by 89%. Addition of a cathepsin G-inhibitor resulted in further inhibition of the secretory response, Addition of phosphoramidon, a drug known to inhibit Pseudom onas aeruginosa elastase, had no effect. We conclude that CF sputum po tently stimulates airway submucosal gland cell secretion. These studie s with protease inhibitors suggest that neutrophil proteases account s ubstantially for the secretagogue activity present in CP sputum,