Recombinant human DNase (rhDNase) influences phospholipid composition, surface activity, rheology and consecutively clearance indices of cystic fibrosis sputum

Abstract

Cystic fibrosis (CF) is caused by mutation in the gene for the CF transmembrane conductance regulator which leads to massive, abnormally viscous, purulent sputum, chronic destructive endobronchitis and early death. Purified recombinant human (rh) DNase can digest extracellular DNA and its inhalation in these patients significantly improves lung function. To evaluate the poorly understood mechanisms, saliva protected sputum from patients treated with and without rhDNase were evaluated. Therapy with rhDNase resulted in a soluble sputum fraction that had a higher percentage of phosphatidylethanolamine, a phospholipid present mainly in cellular membranes, a much lower percentage of phosphatidylcholine, but a higher surface activity. The rigidity was significantly lower and the ratio of viscosity in proportion to elasticity increased. All these data are consistent with an increased clearability of the sputum by coughing, but not by mucociliary activity. Thus the interaction of inhaled rhDNase with the purulent mucus and the endobronchial inflammatory processes may induce changes that result in rheological properties favoring clearance of sputum by cough.