Improved activity of an actin-resistant DNase I variant on the cystic fibrosis airway secretions

In cystic fibrosis (CF), actin and DNA originating from inflammatory cells contribute to the thickness of airway secretions. Actin can bind to DNA-ric h fibers and potently inhibit the enzymatic activity of rhDNase. The In vit ro effects of the actin-resistant rhDNase variant (A114R) were analyzed and compared with those of the wild-type rhDNase. Frozen and thawed CF airway secretions were incubated for 30 min with different concentrations (0.1, 0. 5, 1, 5, or 10 mug/ml) of either actin-resistant rhDNase or wild-type rhDNa se. We observed that both the wild-type and the actin-resistant rhDNase sig nificantly decreased (p < 0.05 and p < 0.001, respectively) the airway secr etion viscosity. The decrease in airway secretion viscosity was significant even at low concentrations (0.1 mug/ml) of the actin-resistant variant. In cubation with the actin-resistant variant resulted in a significant decreas e (p < 0.02) of the airway secretion contact angle and cough transport. A s ignificantly higher (p < 0.01) increase in contact angle and cough transpor t of airway secretions was observed at 10 mug/ml with the actin-resistant v ariant as compared with the wild-type rhDNase. The present study had demons trated that the actin-resistant rhDNase variant (A114R) has an enhanced cap acity to improve the physical properties and cough transport of airway secr etions from patients with cystic fibrosis.