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Cationic Polypeptides Are Required for Antibacterial Activity of Human Airway Fluid¹

Alexander M. Cole^2,*,, Hsiang-I Liao^*,, Olga Stuchlik, Jason Tilan^*,, Jan Pohl and Tomas Ganz^*,

^* Department of Medicine, Division of Pulmonary and Critical Care Medicine, and Will Rogers Institute Pulmonary Research Laboratory, University of California, Los Angeles, School of Medicine, Los Angeles, CA 90095; and Microchemical Facility, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322

In a search for direct evidence leading to the biological relevance of airway secretions in innate host defense, we characterized the antibacterial function of cationic polypeptides within minimally manipulated nasal fluid. In this study, we show that cationic antimicrobial polypeptides are responsible for most of the bactericidal activity of whole nasal fluid. The removal of cationic polypeptides using a cation-exchange resin ablated the activity of nasal fluid against Escherichia coli, Listeria monocytogenes, and Pseudomonas aeruginosa. By using a novel proteomic approach, we identified a dozen cationic peptides and proteins within nasal fluid, all of which either are known antimicrobial polypeptides or have other proposed roles in host defense. Of the three most abundant cationic polypeptides in nasal fluid, lysozyme was more effective than either lactoferrin or secretory leukoprotease inhibitor in restoring the antibacterial activity of the cationic polypeptide-depleted fluid against a mucoid cystic fibrosis isolate of P. aeruginosa.

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