ACTIN-FILAMENTS MEDIATE DNA FIBER FORMATION IN CHRONIC INFLAMMATORY AIRWAY DISEASE

Purulent sputum from patients with chronic obstructive pulmonary disea se has long been known to contain large DNA-rich fibers believed to im pede airu,ay drainage. We present a novel approach to study sputum str ucture using fluorescence microscopy to confirm the presence of large DNA-rich fibers and visualize for the first time filamentous actin in an sputum samples examined from patients with cystic fibrosis and chro nic bronchitis. Both actin and DNA co-localize in the filaments previo usly identified as DNA alone. Treatment of sputum samples with recombi nant human DNase I or the actin-filament-severing protein, gelsolin, b oth 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 bun nies dissolve when treated with either gelsolin or DNase I. These find ings implicate actin-DNA interactions in the pathogenesis of airway di sease and identify both polymers as targets for therapy.