The lactoperoxidase system functions in bacterial clearance of airways

Airway mucus is a complex mixture of secretory products that provides a mul tifaceted defense against pulmonary infection. Mucus contains antimicrobial peptides (e.g., defensins) and enzymes (e.g., lysozyme) although the contr ibution of these to airway sterility has not been tested in vivo. We have p reviously shown that an enzymatically active, heme-containing peroxidase co mprises 1% of the soluble protein in sheep airway secretions, and it has be en hypothesized that this airway peroxidase may function as a biocidal syst em. In this study, we show that sheep airway peroxidase is identical to mil k lactoperoxidase (LPO) and that sheep airway secretions contain thiocyanat e (SCN) at concentrations necessary and sufficient for a functional peroxid ase system that can protect against infection. We also show that airway LPO , like milk LPO, produces the biocidal compound hypothiocyanite (OSCN) in v itro. Finally, we show that in vivo inhibition of airway LPO in sheep leads to a significant decrease in bacterial clearance from the airways. The dat a suggest that the LPO system is a major contributor to airway defenses. Th is discovery may have significant implications for chronic airway colonizat ion seen in respiratory diseases such as cystic fibrosis.