title: Synergistic and additive killing by antimicrobial factors found in human airway surface liquid.
abstract: Airway surface liquid contains multiple factors thought to provide a first line of defense against bacteria deposited in the airways. Although the antimicrobial action of individual factors has been studied, less is known about how they work in combination. We examined the combined action of six antimicrobial peptides found in airway surface liquid. The paired combinations of lysozyme-lactoferrin, lysozyme-secretory leukocyte protease inhibitor (SLPI), and lactoferrin-SLPI were synergistic. The triple combination of lysozyme, lactoferrin, and SLPI showed even greater synergy. Other combinations involving the human beta-defensins, LL-37, and tobramycin (often administered to cystic fibrosis patients by inhalation) were additive. Because the airway surface liquid salt concentration may be elevated in cystic fibrosis patients, we examined the effect of salt on the synergistic combinations. As the ionic strength increased, synergistic interactions were lost. Our data suggest that the antibacterial potency of airway surface liquid may be significantly increased by synergistic and additive interactions between antimicrobial factors. These results also suggest that increased salt concentrations that may exist in cystic fibrosis could inhibit airway defenses by diminishing these synergistic interactions.
authors.affiliation: Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA.
authors.forename: P K
authors.initials: PK
authors.lastname: Singh
authors.forename: B F
authors.initials: BF
authors.lastname: Tack
authors.forename: P B
authors.initials: PB
authors.lastname: McCray
authors.forename: M J
authors.initials: MJ
authors.lastname: Welsh
mesh_terms: D000900:Anti-Bacterial Agents / Q000302:isolation & purification / Q000494:pharmacology*; D023082:Defensins / Q000494:pharmacology; D004347:Drug Interactions; D004357:Drug Synergism; D004926:Escherichia coli / Q000187:drug effects*; D005110:Extracellular Space / Q000737:chemistry / Q000502:physiology; D006801:Humans; D007700:Kinetics; D007781:Lactoferrin / Q000494:pharmacology*; D008895:Milk, Human / Q000737:chemistry / Q000502:physiology; D009113:Muramidase / Q000494:pharmacology*; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D020545:Respiratory Mucosa; D053481:Secretory Leukocyte Peptidase Inhibitor; D014031:Tobramycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D023082:Defensins; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D011994:Recombinant Proteins; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; D009113:Muramidase; D007781:Lactoferrin; D014031:Tobramycin