Recombinant human DNase I reduces the viscosity of cystic fibrosis sputum.

Respiratory distress and progressive lung destruction in cystic fibrosis can be attributed to bacterial persistence and the accumulation of viscous purulent secretions in the airways. More than 30 yr ago it was suggested that the large amounts of DNA in purulent secretions contribute to its viscosity and that bovine pancreatic DNase I could reduce the viscosity. To evaluate the potential clinical utility of recombinant human DNase I (rhDNase) in the treatment of cystic fibrosis, we have cloned, sequenced, and expressed rhDNase. Catalytic amounts of rhDNase greatly reduce the viscosity of purulent cystic fibrosis sputum, transforming it within minutes from a nonflowing viscous gel to a flowing liquid. The reduction in viscosity is associated with a decrease in size of DNA in the sputum. Inhalation of a rhDNase aerosol may be a simple direct approach that will help individuals with cystic fibrosis and other patients with pneumonia or bronchitis to clear their airways of purulent secretions. IMAGES:

囊性纤维化（cystic fibrosis）患者所出现的呼吸窘迫与进行性肺组织破坏，可归因于细菌持续感染以及气道内黏稠脓性分泌物的积聚。早在三十余年前，便有研究指出脓性分泌物中大量的脱氧核糖核酸（DNA）会提升其黏稠度，而牛胰脱氧核糖核酸酶I（bovine pancreatic DNase I）可降低该黏稠度。为评估重组人脱氧核糖核酸酶I（rhDNase）用于囊性纤维化治疗的潜在临床应用价值，我们完成了重组人脱氧核糖核酸酶I的克隆、测序与表达工作。催化剂量的重组人脱氧核糖核酸酶I可显著降低囊性纤维化脓性痰液的黏稠度，使其在数分钟内从无法流动的黏稠凝胶转变为可流动的液体。该黏稠度降低与痰液中DNA片段尺寸的减小存在相关性。吸入重组人脱氧核糖核酸酶I气溶胶，或许是一种简便直接的治疗手段，可帮助囊性纤维化患者以及其他罹患肺炎或支气管炎的患者清除气道内的脓性分泌物。图像资料：