Sheils C A, Käs J, Travassos W, Allen P G, Janmey P A, Wohl M E, Stossel T P
Respiratory Division, Children's Hospital, Boston, Massachusetts, USA.
Am J Pathol. 1996 Mar;148(3):919-27.
Purulent sputum from patients with chronic obstructive pulmonary disease has long been known to contain large DNA-rich fibers believed to impede airway drainage. We present a novel approach to study sputum structure using fluorescence microscopy to confirm the presence of large DNA-rich fibers and visualize for the first time filamentous actin in all sputum samples examined from patients with cystic fibrosis and chronic bronchitis. Both actin and DNA co-localize in the filaments previously identified as DNA alone. Treatment of sputum samples with recombinant human DNase I or the actin-filament-severing protein, gelsolin, both previously found to decrease viscosity, dissolves the sputum fiber bundles. Purified human DNA does not form large fibers alone in vitro but does so in the presence of filamentous actin, and these fiber bundles dissolve when treated with either gelsolin or DNase I. These findings implicate actin-DNA interactions in the pathogenesis of airway disease and identify both polymers as targets for therapy.
长期以来，人们一直知道慢性阻塞性肺疾病患者的脓性痰液中含有大量富含DNA的纤维，据信这些纤维会阻碍气道引流。我们提出了一种利用荧光显微镜研究痰液结构的新方法，以确认大量富含DNA的纤维的存在，并首次在囊性纤维化和慢性支气管炎患者的所有痰液样本中观察到丝状肌动蛋白。肌动蛋白和DNA在先前仅被鉴定为DNA的细丝中共定位。用重组人脱氧核糖核酸酶I或肌动蛋白丝切断蛋白凝溶胶蛋白处理痰液样本，这两种物质先前都被发现可降低粘度，它们能溶解痰液纤维束。纯化的人DNA在体外单独不会形成大纤维，但在丝状肌动蛋白存在的情况下会形成，并且当用凝溶胶蛋白或脱氧核糖核酸酶I处理时，这些纤维束会溶解。这些发现表明肌动蛋白与DNA的相互作用在气道疾病的发病机制中起作用，并确定这两种聚合物都是治疗靶点。
