Poly-l-Lysine Compacts DNA, Kills Bacteria, and Improves Protease Inhibition in Cystic Fibrosis Sputum

• DOI: 10.1164/rccm.201305-0912oc
• Publication Date: 2013-08-15T17:56:24Z
• Authors: Alice V. Dubois; Patrick Midoux; Delphine Gras; Mustapha Si-Tahar; Déborah Bréa; Sylvie Attucci; Mustapha-Kamel Kh...; Reuben Ramphal; Patrice Diot; Francis Gauthier; Virginie Hervé
• Keywords: Neutrophil elastase; Proinflammatory cytokine

Rationale: Neutrophil serine proteases in cystic fibrosis (CF) lung secretions partially resist inhibition by natural and exogenous inhibitors, mostly because DNA impairs their control. Cationic polypeptides display the property of condensing retain antimicrobial properties. We hypothesized that condensation cationic CF sputum would result a better control inflammation infection.Objectives: examined whether poly-l-lysine compact liquefy sputum, improve extracellular it displays antibacterial properties toward CF-associated bacteria.Methods: used fluorogenic methods to measure proteolytic activities protease inhibitors whole homogenates from patients with before after treatment poly-l-lysine. Antibacterial were measured bacterial cultures sputum. Poly-l-lysine toxicity was evaluated aerosolization histologic analysis, flow cytometry, quantification proinflammatory cytokines.Measurements Main Results: compacts DNA, generating liquid phase improves ciliary beating frequency at epithelial surface, allows neutrophil elastase cathepsin G inhibitors. It retains against Pseudomonas aeruginosa Staphylococcus aureus doses induce no mouse aerosol administration.Conclusions: may be an alternative dornase-α added benefits helps deleterious effects extracellularly released has ability kill bacteria