Antigen stasis and airway nitrosative stress in human primary ciliary dyskinesia

Benjamin Gaston, Laura A. Smith, Michael D. Davis, Jessica Saunders, Ivana Daniels, Amjad Horani, Steven L. Brody, Olivia Giddings, Yi Zhao, Nadzeya Marozkina

Research output: Contribution to journalArticlepeer-review

Abstract

Nasal nitric oxide (nNO) is low in most patients with primary ciliary dyskinesia (PCD). Decreased ciliary motion could lead to antigen stasis, increasing oxidant production and NO oxidation in the airways. This could both decrease gas phase NO and increase nitrosative stress. We studied primary airway epithelial cells from healthy controls (HCs) and patients with PCD with several different genotypes. We measured antigen clearance in fenestrated membranes exposed apically to the fluorescently labeled antigen Dermatophagoides pteronyssinus (Derp1-f). We immunoblotted for 3-nitrotyrosine (3-NT) and for oxidative response enzymes. We measured headspace NO above primary airway cells without and with a PCD-causing genotype. We measured nNO and exhaled breath condensate (EBC) H2O2 in vivo. Apical Derp1-f was cleared from HC better than from PCD cells. DUOX1 expression was lower in HC than in PCD cells at baseline and after 24-h Derp1-f exposure. HC cells had less 3-NT and NO3- than PCD cells. However, NO consumption by HC cells was less than that by PCD cells; NO loss was prevented by superoxide dismutase (SOD) and by apocynin. nNO was higher in HCs than in patients with PCD. EBC H2O2 was lower in HC than in patients with PCD. The PCD airway epithelium does not optimally clear antigens and is subject to oxidative and nitrosative stress. Oxidation associated with antigen stasis could represent a therapeutic target in PCD, one with convenient monitoring biomarkers.

Original languageEnglish
Pages (from-to)L468-L476
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume326
Issue number4
DOIs
StatePublished - Apr 2024

Keywords

  • DUOX1
  • nasal NO
  • nitrosative stress
  • oxidation
  • primary ciliary dyskinesia

Fingerprint

Dive into the research topics of 'Antigen stasis and airway nitrosative stress in human primary ciliary dyskinesia'. Together they form a unique fingerprint.

Cite this