Lactoperoxidase and Human Airway Host Defense

Abstract

The lactoperoxidase (LPO) antibiotic system is a well-characterized component of mammary and salivary gland secretions. Because LPO has been shown to function in ovine airways, human airway tissue and secretions were examined for the presence of LPO and its substrate, the anion thiocyanate (SCN-). In addition, human airway secretions were tested for LPO-mediated antibacterial activity, and LPO's activity was assessed against some human airway pathogens. The data showed that normal human airway secretions contained LPO enzyme activity (0.65 +/- 0.09 microg/mg secreted protein; n = 17), and Western blots of secretions demonstrated bands of the expected sizes for LPO. LPO mRNA was detected in trachea by sequencing PCR-amplified cDNA. SCN-, LPO's substrate, was present in undiluted airway secretions at concentrations sufficient for LPO catalysis (0.46 +/- 0.19 mM; n = 8), and diluted secretions contained antibacterial activity with LPO-like properties. Immunocytochemistry localized LPO to submucosal glands in human bronchi. Finally, as expected based on the known antibacterial spectrum of the LPO system, airway secretions showed LPO-dependent activity against Pseudomonas aeruginosa. In addition, the airway LPO system was shown to be effective against Burkholderia cepacia and Haemophilus influenzae. Thus, a functional LPO system exists in human airways and may contribute to airway host defense against infection.

The lactoperoxidase system links anion transport to host defense in cystic fibrosis

“…These levels of H 2 O 2 , added to in vitro peroxidase antibacterial systems, are well below the levels needed for killing of bacteria by H 2 O 2 alone (e.g. [12]). Second, broad screens of antibacterial substances have often focused on components with molecular masses below that of LPO (e.g.…”

“…5 were derived from estimates or measured amounts of enzyme and substrates [12], transport rates (preliminary data, above), and volumes [3] Normal CF Units…”

NADPH oxidases in lung biology and pathology: Host defense enzymes, and more

“…The importance of DUOX2 in thyroid hormone synthesis is supported by clinical observations of hypothyroidism in association with missense mutations in the DUOX2 gene (28,29). DUOX1 and 2 are also expressed in airway and intestinal epithelia, where they may contribute to host defense by a similar cooperative mechanism with lactoperoxidase (LPO), which is secreted by submucosal glands (1,30,31). A structurally related dual oxidase, Udx1, is expressed in sea urchin eggs and is activated upon fertilization to produce H 2 O 2 which stimulates ovoperoxidase-mediated protein cross-linking within the fertilization envelope (32).…”

“…The variable expression of DUOX1/2 by Th1 and Th2 cytokines suggests divergent roles of these enzymes in either innate or adaptive immune host defenses. (30,100). Direct experimental evidence for the role of DUOX in fueling this LPO-SCN − -mediated antimicrobial host defense system was recently obtained in in vitro studies of rat and bovine tracheal epithelial cells (86).…”

The antioxidant role of thiocyanate in the pathogenesis of cystic fibrosis and other inflammation-related diseases

“…SCN Ϫ enters an airway epithelial cell via transporters in its basolateral membrane, and reaches the airway lumen via CFTR in its apical membrane (23). This transepithelial movement results in 460 M SCN Ϫ in the airway secretions, substantially higher than the plasma concentration (24). SCN Ϫ release is absent in the epithelial cells missing CFTR activity (25,26 (Fig.…”