Pepsin Triggers Neutrophil Migration Across Acid Damaged Lung Epithelium. Sci Rep 2019 Sep 24;9(1):13778
Date
09/26/2019Pubmed ID
31551494Pubmed Central ID
PMC6760148DOI
10.1038/s41598-019-50360-4Scopus ID
2-s2.0-85072622956 (requires institutional sign-in at Scopus site) 25 CitationsAbstract
Pepsin represents a potential biomarker for extraesophageal reflux disease when detected in airways, however a direct role for pepsin in lung dysfunction has not been clearly established. Children experiencing gastroesophageal and extraesophageal reflux are often prescribed proton pump inhibitors (PPIs) to reduce gastric acid associated damage to esophageal and airway mucosa. The potential of pepsin and gastric fluid, from children that were either on or off PPI therapy, to cause inflammation and damage using a human in vitro co-culture model of the airway mucosa was evaluated herein. Exposure of the airway model to acidic solutions caused cellular damage and loss of viability, however, acid alone did not disrupt barrier integrity or instigate neutrophil trans-epithelial migration without pepsin. Gastric fluid from patients on PPI therapy exhibited only a slightly higher pH yet had significantly higher concentrations of pepsin and elicited more barrier disruption and neutrophil trans-epithelial migration compared to gastric fluid from patients off PPIs. Inflammatory and damaging responses observed with gastric fluid from patients on PPIs were largely driven by pepsin. These results indicate the potential for PPI usage to raise concentrations of pepsin in gastric fluid, which may enhance the pathological impact of micro-aspirations in children with extraesophageal reflux.
Author List
Hurley BP, Jugo RH, Snow RF, Samuels TL, Yonker LM, Mou H, Johnston N, Rosen RAuthor
Nikki Johnston PhD Professor in the Otolaryngology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Bile Acids and Salts
Cell Line
Cell Movement
Child
Epithelium
Esophageal pH Monitoring
Esophagus
Female
Gastric Acid
Gastroesophageal Reflux
Humans
Hydrogen-Ion Concentration
Inflammation
Male
Neutrophils
Pepsin A
Proton Pump Inhibitors
Young Adult
