Open AccessAcid exposure disrupts mucus secretion and impairs mucociliary transport in neonatal piglet airways
Author(s) -
Yan Shin J. Liao,
Shin Ping Kuan,
Maria Valentina Guevara,
E. N. Collins,
Kalina R. Atanasova,
Joshua S. Dadural,
Kevin Vogt,
Veronica Schurmann,
Laura Bravo,
Eda Eken,
Mariana Sponchiado,
Leah R. Reznikov
Publication year - 2020
Publication title -
american journal of physiology. lung cellular and molecular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.892
H-Index - 163
eISSN - 1522-1504
pISSN - 1040-0605
DOI - 10.1152/ajplung.00025.2020
Subject(s) - mucus , submucosal glands , cystic fibrosis , airway , mucin , mucociliary clearance , secretion , goblet cell , respiratory tract , airway obstruction , chemistry , lung , respiratory system , medicine , pathology , biology , anesthesia , epithelium , ecology
Tenacious mucus produced by tracheal and bronchial submucosal glands is a defining feature of several airway diseases, including cystic fibrosis (CF). Airway acidification as a driving force of CF airway pathology has been controversial. Here we tested the hypothesis that transient airway acidification produces pathologic mucus and impairs mucociliary transport. We studied pigs challenged with intra-airway acid. Acid had a minimal effect on mucus properties under basal conditions. However, cholinergic stimulation in acid-challenged pigs revealed retention of mucin 5B (MUC5B) in the submucosal glands, decreased concentrations of MUC5B in the lung lavage fluid, and airway obstruction. To more closely mimic a CF-like environment, we also examined mucus secretion and transport following cholinergic stimulation under diminished bicarbonate and chloride transport conditions ex vivo. Under these conditions, airways from acid-challenged pigs displayed extensive mucus films and decreased mucociliary transport. Pretreatment with diminazene aceturate, a small molecule with ability to inhibit acid detection through blockade of the acid-sensing ion channel (ASIC) at the doses provided, did not prevent acid-induced pathologic mucus or transport defects but did mitigate airway obstruction. These findings suggest that transient airway acidification early in life has significant impacts on mucus secretion and transport properties. Furthermore, they highlight diminazene aceturate as an agent that might be beneficial in alleviating airway obstruction.