Concentration of the Antibacterial Precursor Thiocyanate in Cystic Fibrosis Airway Secretions

Overview

Journal Free Radic Biol Med

Specialties Biochemistry
Biology
General Medicine

Date 2011 Feb 22

PMID 21334431

Citations 34

Authors

Daniel Lorentzen

Lakshmi Durairaj

Alejandro A Pezzulo

Yoko Nakano

Janice Launspach

David A Stoltz

Gideon Zamba

Paul B McCray Jr

Joseph Zabner

Michael J Welsh

William M Nauseef

Botond Banfi

Affiliations

Soon will be listed here.

Abstract

A recently discovered enzyme system produces antibacterial hypothiocyanite (OSCN(-)) in the airway lumen by oxidizing the secreted precursor thiocyanate (SCN(-)). Airway epithelial cultures have been shown to secrete SCN(-) in a CFTR-dependent manner. Thus, reduced SCN(-) availability in the airway might contribute to the pathogenesis of cystic fibrosis (CF), a disease caused by mutations in the CFTR gene and characterized by an airway host defense defect. We tested this hypothesis by analyzing the SCN(-) concentration in the nasal airway surface liquid (ASL) of CF patients and non-CF subjects and in the tracheobronchial ASL of CFTR-ΔF508 homozygous pigs and control littermates. In the nasal ASL, the SCN(-) concentration was ~30-fold higher than in serum independent of the CFTR mutation status of the human subject. In the tracheobronchial ASL of CF pigs, the SCN(-) concentration was somewhat reduced. Among human subjects, SCN(-) concentrations in the ASL varied from person to person independent of CFTR expression, and CF patients with high SCN(-) levels had better lung function than those with low SCN(-) levels. Thus, although CFTR can contribute to SCN(-) transport, it is not indispensable for the high SCN(-) concentration in ASL. The correlation between lung function and SCN(-) concentration in CF patients may reflect a beneficial role for SCN(-).

Citing Articles

CFTR dysfunction leads to defective bacterial eradication on cystic fibrosis airways.

Wu M, Chen J Front Physiol. 2024; 15:1385661.

PMID: 38699141 PMC: 11063615. DOI: 10.3389/fphys.2024.1385661.

The therapeutic potential of thiocyanate and hypothiocyanous acid against pulmonary infections.

Ashtiwi N, Kim S, Chandler J, Rada B Free Radic Biol Med. 2024; 219:104-111.

PMID: 38608822 PMC: 11088529. DOI: 10.1016/j.freeradbiomed.2024.04.217.

Substrate-dependent metabolomic signatures of myeloperoxidase activity in airway epithelial cells: Implications for early cystic fibrosis lung disease.

Kim S, Shapiro J, Cottrill K, Collins G, Shanthikumar S, Rao P Free Radic Biol Med. 2023; 206:180-190.

PMID: 37356776 PMC: 10513041. DOI: 10.1016/j.freeradbiomed.2023.06.021.

Cystic Fibrosis Reprograms Airway Epithelial IL-33 Release and Licenses IL-33-Dependent Inflammation.

Cook D, Thomas C, Wu A, Rusznak M, Zhang J, Zhou W Am J Respir Crit Care Med. 2023; 207(11):1486-1497.

PMID: 36952660 PMC: 10263140. DOI: 10.1164/rccm.202211-2096OC.

Hypothiocyanite and host-microbe interactions.

Meredith J, Gray M Mol Microbiol. 2023; 119(3):302-311.

PMID: 36718113 PMC: 10320662. DOI: 10.1111/mmi.15025.

References

El-Chemaly S, Salathe M, Baier S, Conner G, Forteza R . Hydrogen peroxide-scavenging properties of normal human airway secretions. Am J Respir Crit Care Med. 2002; 167(3):425-30. DOI: 10.1164/rccm.200206-531OC. View

Doring G, Gulbins E . Cystic fibrosis and innate immunity: how chloride channel mutations provoke lung disease. Cell Microbiol. 2008; 11(2):208-16. DOI: 10.1111/j.1462-5822.2008.01271.x. View

Forteza R, Salathe M, Miot F, Forteza R, Conner G . Regulated hydrogen peroxide production by Duox in human airway epithelial cells. Am J Respir Cell Mol Biol. 2005; 32(5):462-9. DOI: 10.1165/rcmb.2004-0302OC. View

Zabner J, Scheetz T, Almabrazi H, Casavant T, Huang J, Keshavjee S . CFTR DeltaF508 mutation has minimal effect on the gene expression profile of differentiated human airway epithelia. Am J Physiol Lung Cell Mol Physiol. 2005; 289(4):L545-53. DOI: 10.1152/ajplung.00065.2005. View

Wesley U, Bove P, Hristova M, McCarthy S, van der Vliet A . Airway epithelial cell migration and wound repair by ATP-mediated activation of dual oxidase 1. J Biol Chem. 2006; 282(5):3213-20. DOI: 10.1074/jbc.M606533200. View

Nakagami Y, Favoreto Jr S, Zhen G, Park S, Nguyenvu L, Kuperman D . The epithelial anion transporter pendrin is induced by allergy and rhinovirus infection, regulates airway surface liquid, and increases airway reactivity and inflammation in an asthma model. J Immunol. 2008; 181(3):2203-10. PMC: 2491716. DOI: 10.4049/jimmunol.181.3.2203. View

Chapman A, Morrissey B, Vasu V, Juarez M, Houghton J, Li C . Myeloperoxidase-dependent oxidative metabolism of nitric oxide in the cystic fibrosis airway. J Cyst Fibros. 2010; 9(2):84-92. PMC: 3118565. DOI: 10.1016/j.jcf.2009.10.001. View

Xu Y, Szep S, Lu Z . The antioxidant role of thiocyanate in the pathogenesis of cystic fibrosis and other inflammation-related diseases. Proc Natl Acad Sci U S A. 2009; 106(48):20515-9. PMC: 2777967. DOI: 10.1073/pnas.0911412106. View

Morrissey B, Schilling K, Weil J, Silkoff P, Rodman D . Nitric oxide and protein nitration in the cystic fibrosis airway. Arch Biochem Biophys. 2002; 406(1):33-9. DOI: 10.1016/s0003-9861(02)00427-7. View

10.

Conner G, Wijkstrom-Frei C, Randell S, Fernandez V, Salathe M . The lactoperoxidase system links anion transport to host defense in cystic fibrosis. FEBS Lett. 2007; 581(2):271-8. PMC: 1851694. DOI: 10.1016/j.febslet.2006.12.025. View

11.

Rada B, Geiszt M, Kaldi K, Timar C, Ligeti E . Dual role of phagocytic NADPH oxidase in bacterial killing. Blood. 2004; 104(9):2947-53. DOI: 10.1182/blood-2004-03-1005. View

12.

Rogers C, Hao Y, Rokhlina T, Samuel M, Stoltz D, Li Y . Production of CFTR-null and CFTR-DeltaF508 heterozygous pigs by adeno-associated virus-mediated gene targeting and somatic cell nuclear transfer. J Clin Invest. 2008; 118(4):1571-7. PMC: 2265103. DOI: 10.1172/JCI34773. View

13.

Jones K, Hegab A, Hillman B, Simpson K, Jinkins P, Grisham M . Elevation of nitrotyrosine and nitrate concentrations in cystic fibrosis sputum. Pediatr Pulmonol. 2000; 30(2):79-85. DOI: 10.1002/1099-0496(200008)30:2<79::aid-ppul1>3.0.co;2-1. View

14.

Geiszt M, Witta J, Baffi J, Lekstrom K, Leto T . Dual oxidases represent novel hydrogen peroxide sources supporting mucosal surface host defense. FASEB J. 2003; 17(11):1502-4. DOI: 10.1096/fj.02-1104fje. View

15.

Meyerholz D, Stoltz D, Namati E, Ramachandran S, Pezzulo A, Smith A . Loss of cystic fibrosis transmembrane conductance regulator function produces abnormalities in tracheal development in neonatal pigs and young children. Am J Respir Crit Care Med. 2010; 182(10):1251-61. PMC: 3001264. DOI: 10.1164/rccm.201004-0643OC. View

16.

Gerson C, Sabater J, Scuri M, Torbati A, Coffey R, Abraham J . The lactoperoxidase system functions in bacterial clearance of airways. Am J Respir Cell Mol Biol. 2000; 22(6):665-71. DOI: 10.1165/ajrcmb.22.6.3980. View

17.

Boots A, Hristova M, Kasahara D, Haenen G, Bast A, van der Vliet A . ATP-mediated activation of the NADPH oxidase DUOX1 mediates airway epithelial responses to bacterial stimuli. J Biol Chem. 2009; 284(26):17858-67. PMC: 2719424. DOI: 10.1074/jbc.M809761200. View

18.

Schwarzer C, Machen T, Illek B, Fischer H . NADPH oxidase-dependent acid production in airway epithelial cells. J Biol Chem. 2004; 279(35):36454-61. DOI: 10.1074/jbc.M404983200. View

19.

Wang J, Mahmud S, Nguyen J, Slungaard A . Thiocyanate-dependent induction of endothelial cell adhesion molecule expression by phagocyte peroxidases: a novel HOSCN-specific oxidant mechanism to amplify inflammation. J Immunol. 2006; 177(12):8714-22. DOI: 10.4049/jimmunol.177.12.8714. View

20.

Grasemann H, Ioannidis I, Tomkiewicz R, De Groot H, Rubin B, Ratjen F . Nitric oxide metabolites in cystic fibrosis lung disease. Arch Dis Child. 1998; 78(1):49-53. PMC: 1717443. DOI: 10.1136/adc.78.1.49. View