title: The lactoperoxidase system functions in bacterial clearance of airways.
abstract: Airway mucus is a complex mixture of secretory products that provides a multifaceted defense against pulmonary infection. Mucus contains antimicrobial peptides (e.g., defensins) and enzymes (e.g., lysozyme) although the contribution of these to airway sterility has not been tested in vivo. We have previously shown that an enzymatically active, heme-containing peroxidase comprises 1% of the soluble protein in sheep airway secretions, and it has been hypothesized that this airway peroxidase may function as a biocidal system. In this study, we show that sheep airway peroxidase is identical to milk lactoperoxidase (LPO) and that sheep airway secretions contain thiocyanate (SCN(-)) at concentrations necessary and sufficient for a functional peroxidase system that can protect against infection. We also show that airway LPO, like milk LPO, produces the biocidal compound hypothiocyanite (OSCN(-)) in vitro. Finally, we show that in vivo inhibition of airway LPO in sheep leads to a significant decrease in bacterial clearance from the airways. The data suggest that the LPO system is a major contributor to airway defenses. This discovery may have significant implications for chronic airway colonization seen in respiratory diseases such as cystic fibrosis.
authors.affiliation: Department of Cell Biology and Anatomy and Division of Pulmonary and Critical Care Medicine, University of Miami School of Medicine, Miami, Florida 33101, USA. gconner@miami.edu
authors.forename: C
authors.initials: C
authors.lastname: Gerson
authors.forename: J
authors.initials: J
authors.lastname: Sabater
authors.forename: M
authors.initials: M
authors.lastname: Scuri
authors.forename: A
authors.initials: A
authors.lastname: Torbati
authors.forename: R
authors.initials: R
authors.lastname: Coffey
authors.forename: J W
authors.initials: JW
authors.lastname: Abraham
authors.forename: I
authors.initials: I
authors.lastname: Lauredo
authors.forename: R
authors.initials: R
authors.lastname: Forteza
authors.forename: A
authors.initials: A
authors.lastname: Wanner
authors.forename: M
authors.initials: M
authors.lastname: Salathe
authors.forename: W M
authors.initials: WM
authors.lastname: Abraham
authors.forename: G E
authors.initials: GE
authors.lastname: Conner
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D017931:DNA Primers; D018076:DNA, Complementary / Q000032:analysis; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D066298:In Vitro Techniques; D007784:Lactoperoxidase / Q000235:genetics* / Q000378:metabolism*; D008168:Lung / Q000201:enzymology / Q000382:microbiology; D016978:Mannheimia haemolytica; D008892:Milk / Q000201:enzymology; D008969:Molecular Sequence Data; D010326:Pasteurella Infections / Q000378:metabolism; D018410:Pneumonia, Bacterial / Q000201:enzymology* / Q000382:microbiology; D012333:RNA, Messenger / Q000032:analysis; D020545:Respiratory Mucosa / Q000201:enzymology* / Q000378:metabolism / Q000382:microbiology; D012756:Sheep; D013861:Thiocyanates / Q000378:metabolism
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D012333:RNA, Messenger; D013861:Thiocyanates; C014607:hypothiocyanite ion; D007784:Lactoperoxidase