Bicarbonate Effects on Antibacterial Immunity and Mucus Glycobiology in the Cystic Fibrosis Lung: A Review With Selected Experimental Observations

Abstract. The primary defect in cystic fibrosis (CF) is abnormal chloride and bicarbonate transport in the CF transmembrane conductance regulator epithelial ion channel. The apical surface of the respiratory tract is lined by an airway surface liquid (ASL) layer composed of mucin comprising mainly M...

Full description

Bibliographic Details
Main Authors: Ruth Siew, Tzung-Lin Ou, Samira Dahesh, Kathryn Akong, Victor Nizet
Format: Article
Language:English
Published: Wolters Kluwer Health 2022-09-01
Series:Infectious Microbes & Diseases
Online Access:http://journals.lww.com/10.1097/IM9.0000000000000101
_version_ 1828107919797780480
author Ruth Siew
Tzung-Lin Ou
Samira Dahesh
Kathryn Akong
Victor Nizet
author_facet Ruth Siew
Tzung-Lin Ou
Samira Dahesh
Kathryn Akong
Victor Nizet
author_sort Ruth Siew
collection DOAJ
description Abstract. The primary defect in cystic fibrosis (CF) is abnormal chloride and bicarbonate transport in the CF transmembrane conductance regulator epithelial ion channel. The apical surface of the respiratory tract is lined by an airway surface liquid (ASL) layer composed of mucin comprising mainly MUC5A and MUC5B glycoproteins. ASL homeostasis depends on sodium bicarbonate secretion into the airways and secretion deficits alter mucus properties leading to airway obstruction, inflammation and infections. Downstream effects of abnormal ion transport in the lungs include altered intrinsic immune defenses. We observed that neutrophils killed Pseudomonas aeruginosa more efficiently when it had been exposed to sodium bicarbonate, and formation of neutrophil extracellular traps by neutrophils was augmented in the presence of increasing bicarbonate concentrations. Physiological levels of bicarbonate sensitized P. aeruginosa to the antimicrobial peptide cathelicidin LL-37, which is present in both lung ASL and neutrophil extracellular traps. Sodium bicarbonate has various uses in clinical medicine and in the care of CF patients and could be further explored as a therapeutic adjunct against Pseudomonas infections.
first_indexed 2024-04-11T10:38:31Z
format Article
id doaj.art-ea7e13c8a93e4c2b829d32bc8a302866
institution Directory Open Access Journal
issn 2641-5917
language English
last_indexed 2024-04-11T10:38:31Z
publishDate 2022-09-01
publisher Wolters Kluwer Health
record_format Article
series Infectious Microbes & Diseases
spelling doaj.art-ea7e13c8a93e4c2b829d32bc8a3028662022-12-22T04:29:14ZengWolters Kluwer HealthInfectious Microbes & Diseases2641-59172022-09-014310311010.1097/IM9.0000000000000101202209000-00004Bicarbonate Effects on Antibacterial Immunity and Mucus Glycobiology in the Cystic Fibrosis Lung: A Review With Selected Experimental ObservationsRuth Siew0Tzung-Lin Ou1Samira Dahesh2Kathryn Akong3Victor Nizet4Author affiliations: 1 Department of Pediatrics, University of California San Diego, La Jolla, California, USA2 School of Medicine, China Medical University, Taichung, TaiwanAuthor affiliations: 1 Department of Pediatrics, University of California San Diego, La Jolla, California, USAAuthor affiliations: 1 Department of Pediatrics, University of California San Diego, La Jolla, California, USAAuthor affiliations: 1 Department of Pediatrics, University of California San Diego, La Jolla, California, USAAbstract. The primary defect in cystic fibrosis (CF) is abnormal chloride and bicarbonate transport in the CF transmembrane conductance regulator epithelial ion channel. The apical surface of the respiratory tract is lined by an airway surface liquid (ASL) layer composed of mucin comprising mainly MUC5A and MUC5B glycoproteins. ASL homeostasis depends on sodium bicarbonate secretion into the airways and secretion deficits alter mucus properties leading to airway obstruction, inflammation and infections. Downstream effects of abnormal ion transport in the lungs include altered intrinsic immune defenses. We observed that neutrophils killed Pseudomonas aeruginosa more efficiently when it had been exposed to sodium bicarbonate, and formation of neutrophil extracellular traps by neutrophils was augmented in the presence of increasing bicarbonate concentrations. Physiological levels of bicarbonate sensitized P. aeruginosa to the antimicrobial peptide cathelicidin LL-37, which is present in both lung ASL and neutrophil extracellular traps. Sodium bicarbonate has various uses in clinical medicine and in the care of CF patients and could be further explored as a therapeutic adjunct against Pseudomonas infections.http://journals.lww.com/10.1097/IM9.0000000000000101
spellingShingle Ruth Siew
Tzung-Lin Ou
Samira Dahesh
Kathryn Akong
Victor Nizet
Bicarbonate Effects on Antibacterial Immunity and Mucus Glycobiology in the Cystic Fibrosis Lung: A Review With Selected Experimental Observations
Infectious Microbes & Diseases
title Bicarbonate Effects on Antibacterial Immunity and Mucus Glycobiology in the Cystic Fibrosis Lung: A Review With Selected Experimental Observations
title_full Bicarbonate Effects on Antibacterial Immunity and Mucus Glycobiology in the Cystic Fibrosis Lung: A Review With Selected Experimental Observations
title_fullStr Bicarbonate Effects on Antibacterial Immunity and Mucus Glycobiology in the Cystic Fibrosis Lung: A Review With Selected Experimental Observations
title_full_unstemmed Bicarbonate Effects on Antibacterial Immunity and Mucus Glycobiology in the Cystic Fibrosis Lung: A Review With Selected Experimental Observations
title_short Bicarbonate Effects on Antibacterial Immunity and Mucus Glycobiology in the Cystic Fibrosis Lung: A Review With Selected Experimental Observations
title_sort bicarbonate effects on antibacterial immunity and mucus glycobiology in the cystic fibrosis lung a review with selected experimental observations
url http://journals.lww.com/10.1097/IM9.0000000000000101
work_keys_str_mv AT ruthsiew bicarbonateeffectsonantibacterialimmunityandmucusglycobiologyinthecysticfibrosislungareviewwithselectedexperimentalobservations
AT tzunglinou bicarbonateeffectsonantibacterialimmunityandmucusglycobiologyinthecysticfibrosislungareviewwithselectedexperimentalobservations
AT samiradahesh bicarbonateeffectsonantibacterialimmunityandmucusglycobiologyinthecysticfibrosislungareviewwithselectedexperimentalobservations
AT kathrynakong bicarbonateeffectsonantibacterialimmunityandmucusglycobiologyinthecysticfibrosislungareviewwithselectedexperimentalobservations
AT victornizet bicarbonateeffectsonantibacterialimmunityandmucusglycobiologyinthecysticfibrosislungareviewwithselectedexperimentalobservations