Activity of abundant antimicrobials of the human airway

Human airways produce several antimicrobial factors; the most abundant are lysozyme and lactoferrin. Despite their likely importance in preventing inf ection, and their possible key role in the pathogenesis of cystic fibrosis (CF), we know little about their antibacterial activity in the context of t he CF airway. We found that abundant airway antimicrobial factors kill comm on CF pathogens, although Burkholderia was relatively resistant. To study t he antibacterial activity, we developed a rapid, sensitive, and quantitativ e in vitro luminescence assay. Because NaCl concentrations may be elevated in CF airway surface liquid, we tested the effect of salt on antibacterial activity. Activity of individual factors and of airway lavage fluid was inh ibited by high ionic strength, and it was particularly sensitive to divalen t cations. However, it was not inhibited by nonionic osmolytes and thus did not require hypotonic liquid. The inhibition by ionic strength could be pa rtially compensated by increased concentrations of antibacterial actors, th us there was no one unique salt concentration for inhibition. CF airway sec retions also contain abundant mucin and elastase; however, these had no eff ect on antibacterial activity of lysozyme, lactoferrin, or airway lavage fl uids. When studied at low NaCl concentrations, CF and non-CF airway lavage fluids contained similar levels of antibacterial activity. These results su ggest approaches toward developing treatments aimed at preventing or reduci ng airway infections in individuals with CF.