title: Post-secretory fate of host defence components in mucus.
abstract: Airway mucus is a complex mixture of secretory products that provide a multifaceted defence against infection. Among many antimicrobial substances, mucus contains a peroxidase identical to milk lactoperoxidase (LPO) that is produced by goblet cells and submucosal glands. Airway secretions contain the substrates for LPO, namely thiocyanate and hydrogen peroxide, at concentrations sufficient for production of the biocidal compound hypothiocyanite, a fact confirmed by us in vitro. In vivo, inhibition of airway LPO in sheep significantly inhibits bacterial clearance, suggesting that the LPO system is a major contributor to host defences. Since secretory products including LPO are believed to be steadily removed by mucociliary clearance, their amount and availability on the surface is thought to be controlled solely by secretion. In contrast to this paradigm, new data suggest that LPO and other substances are retained at the ciliary border of the airway epithelium by binding to surface-associated hyaluronan, thereby providing an apical, fully active enzyme pool. Thus, hyaluronan, secreted from submucosal gland cells, plays a previously unrecognized pivotal role in mucosal host defence by retaining LPO and possibly other substances important for first line host defence at the apical surface 'ready for use' and protected from ciliary clearance.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, University of Miami School of Medicine, R-47, 1600 NW 10th Ave, RMSB 7063a, Miami, FL 33136, USA.
authors.forename: Matthias
authors.initials: M
authors.lastname: Salathe
authors.forename: Rosanna
authors.initials: R
authors.lastname: Forteza
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Conner
mesh_terms: D000818:Animals; D001249:Asthma / Q000201:enzymology; D002417:Cattle; D002923:Cilia / Q000502:physiology; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism; D007610:Kallikreins / Q000502:physiology; D007784:Lactoperoxidase / Q000502:physiology; D009077:Mucins / Q000378:metabolism; D009093:Mucus / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000201:enzymology; D012137:Respiratory System / Q000276:immunology* / Q000503:physiopathology; D012141:Respiratory Tract Infections / Q000276:immunology; D012756:Sheep; D013861:Thiocyanates / Q000378:metabolism
chemical_list: D009077:Mucins; D013861:Thiocyanates; D006820:Hyaluronic Acid; D007784:Lactoperoxidase; D007610:Kallikreins