Antigen stasis and airway nitrosative stress in human primary ciliary dyskinesia.

INTRODUCTION: Nasal NO (nNO) is low in most Primary Ciliary Dyskinesia (PCD) patients. Decreased ciliary motion could lead to antigen stasis, increasing oxidant production; and NO oxidation in the airways could both decrease gas phase NO and increase nitrosative stress.

MATERIALS AND METHODS: We studied primary airway epithelial cells from healthy controls (HC) and PCD patients with several different genotypes. We measured antigen clearance in fenestrated membranes exposed apically to fluorescently- labeled antigen Dermatophagoiedes 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) H2 O2 in vivo.

RESULTS: 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 PCD patients. EBC H2 O2 was lower in HC than in PCD patients.

CONCLUSIONS: 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.