Pepsin Triggers Neutrophil Migration Across Acid Damaged Lung Epithelium

Bryan P Hurley1, Rebecca H Jugo2,3, Ryan F Snow2

  • 1Department of Pediatrics, Mucosal Immunology & Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. bphurley@mgh.harvard.edu.

Scientific Reports
|September 26, 2019
PubMed

Insights

Proton pump inhibitors (PPIs) may increase pepsin in reflux fluid, potentially worsening lung damage from micro-aspirations in children with extraesophageal reflux disease.

Area of Science:

  • Gastroenterology
  • Pulmonology
  • Cell Biology

Background:

  • Pepsin in airways is a biomarker for extraesophageal reflux disease (EERD).
  • The direct role of pepsin in lung dysfunction remains unclear.
  • Proton pump inhibitors (PPIs) are commonly used to treat reflux in children.

Purpose of the Study:

  • To evaluate the inflammatory and damaging potential of pepsin and gastric fluid in a human airway co-culture model.
  • To compare the effects of gastric fluid from children on and off PPI therapy.

Main Methods:

  • A human in vitro co-culture model of airway mucosa was exposed to acidic solutions and gastric fluid.
  • Cellular damage, viability, barrier integrity, and neutrophil migration were assessed.
  • Gastric fluid pH and pepsin concentration were measured.

Main Results:

  • Acidic solutions caused damage, but pepsin was required to disrupt barrier integrity and induce neutrophil migration.
  • Gastric fluid from children on PPIs had higher pepsin concentrations and caused more barrier disruption and neutrophil migration than fluid from children off PPIs.
  • Pepsin was the primary driver of inflammatory and damaging responses in gastric fluid from PPI-treated patients.

Conclusions:

  • PPI use may increase pepsin concentrations in gastric fluid.
  • Elevated pepsin may enhance the pathological impact of micro-aspirations in children with EERD.
  • Pepsin, not just acid, plays a critical role in reflux-induced airway damage.

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