title: Enhancement of Pulmozyme activity in purulent sputum by combination with poly-aspartic acid or gelsolin.
abstract: BACKGROUND
  DNase (Pulmozyme) effectiveness in cystic fibrosis treatment is in some cases limited by its inability to access DNA trapped within bundles in highly viscous fluids that also contain actin. Dissociating DNA-containing bundles using actin depolymerizing agents and polyanions has potential to increase DNase efficacy.
  
  
  METHODS
  Fluorescence measurements of YOYO-1 and a rheological creep-recovery test quantified DNA content and viscoelasticity in 150 sputum samples from adult CF patients and their susceptibility to fluidization by DNase1, alone and in combination with gelsolin and poly-aspartate (p-Asp). Fluidization of sputum by these agents is compared to their capacity to increase antibacterial activity in sputum, measured using a luminescent Pseudomonas aeruginosa strain and a bacterial killing assay.
  
  
  RESULTS
  The polyanion p-Asp (1-50 μg/g of sputum), the actin severing protein gelsolin (10-90 μg/g) and their combination enhance the ability of DNase 1 to increase the abnormally low mechanical compliance of CF sputum and to promote bacterial killing in sputum by colistin and tobramycin, two antibiotics commonly used to treat CF.
  
  
  CONCLUSIONS
  Addition of low concentrations of p-ASP or gelsolin can increase the therapeutic value of Pulmozyme (DNase 1).
authors: Department of Physiology and the Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: buckirobert@gmail.com.
authors: Robert
authors: R
authors: Bucki
authors: Department of Physiology and the Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA, USA.
authors: Katrina
authors: K
authors: Cruz
authors: Department of Physiology and the Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA, USA.
authors: Katarzyna
authors: K
authors: Pogoda
authors: Department of Physiology and the Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA, USA.
authors: Ashley
authors: A
authors: Eggert
authors: Department of Physiology and the Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA, USA.
authors: LiKang
authors: L
authors: Chin
authors: Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania, Philadelphia, PA, USA.
authors: Marianne
authors: M
authors: Ferrin
authors: Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania, Philadelphia, PA, USA.
authors: Giovanna
authors: G
authors: Imbesi
authors: Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania, Philadelphia, PA, USA.
authors: Denis
authors: D
authors: Hadjiliadis
authors: Department of Physiology and the Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA, USA.
authors: Paul A
authors: PA
authors: Janmey
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D003187:Compliance; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000378:metabolism* / Q000382:microbiology; D003850:Deoxyribonuclease I / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D018260:Gelsolin / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000494:pharmacology*; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000378:metabolism* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000302:isolation & purification; D011994:Recombinant Proteins / Q000494:pharmacology; D013183:Sputum / Q000737:chemistry*; D013492:Suppuration / Q000382:microbiology; D055815:Young Adult
chemical_list: D018260:Gelsolin; D010455:Peptides; D011994:Recombinant Proteins; C017645:polyaspartate; D003850:Deoxyribonuclease I; C568813:dornase alfa
keywords: Cystic fibrosis; Extracellular DNA; F-actin; Gelsolin; Poly-aspartic acid