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

American Journal of Respiratory and Critical Care Medicine
J M ZahmE Puchelle

Abstract

In cystic fibrosis (CF), actin and DNA originating from inflammatory cells contribute to the thickness of airway secretions. Actin can bind to DNA-rich fibers and potently inhibit the enzymatic activity of rhDNase. The in vitro 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 microg/ml) of either actin-resistant rhDNase or wild-type rhDNase. We observed that both the wild-type and the actin-resistant rhDNase significantly decreased (p < 0.05 and p < 0.001, respectively) the airway secretion viscosity. The decrease in airway secretion viscosity was significant even at low concentrations (0.1 microg/ml) of the actin-resistant variant. Incubation with the actin-resistant variant resulted in a significant decrease (p < 0.02) of the airway secretion contact angle and cough transport. A significantly higher (p < 0.01) increase in contact angle and cough transport of airway secretions was observed at 10 microg/ml with the actin-resistant variant as compared with the wild-type rhDNase. The present study had demonstrated that the actin-resistant rhDNas...Continue Reading

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Citations

Jun 17, 2011·The Journal of Membrane Biology·Vasily V Kuvichkin
Mar 5, 2002·American Journal of Respiratory and Critical Care Medicine·Martin J Tobin
Aug 14, 2012·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·Junko FujiharaHaruo Takeshita
Nov 29, 2005·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·Junko FujiharaHaruo Takeshita
Oct 15, 2011·Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society·Reinhard ManzenreiterDominik Hartl
Apr 4, 2021·Biomolecules·Danila DelfinoRiccardo Percudani

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