title: The role of pepsin in acid injury to esophageal epithelium.
abstract: OBJECTIVE
  The development of reflux esophagitis in humans is a process resulting from esophageal exposure to refluxed gastric contents. There is no doubt that damage to the esophageal epithelium requires exposure to gastric acid; however, the role of refluxed pepsin as contributor to this damage seems to be underappreciated.
  
  
  METHODS
  The role of physiological concentrations of pepsin was examined in Ussing chambered rabbit esophageal epithelium and in cultured esophageal epithelial cells.
  
  
  RESULTS
  The results of this investigation reaffirmed the ability of pepsin to increase the rate and degree of esophageal cell and tissue damage at acidic pH, although the range of activity was limited to pH < 3.0. Moreover, the increased rate of tissue damage by acidified pepsin rapidly (within 15 min) produced a lesion that was irreversible, whereas, in a similar time frame, acid alone produced a lesion that was completely reversible. This early lesion by acidified pepsin was localized by performance of mannitol fluxes in apparently undamaged esophageal epithelium on light microscopy to the intercellular junctional complex. Further acid produced similar degrees of cell killing as acidified pepsin at pH < 3.0 in rabbit esophageal epithelial cells in suspension but not when growing on coverslips or present within intact epithelium.
  
  
  CONCLUSIONS
  These studies suggest that acidified pepsin plays a key role in the development of reflux esophagitis by producing an early irreversible lesion that results in an increase in paracellular permeability, which indirect evidence suggests is due to damage to the junctional complex. The irreversibility of the increase in paracellular permeability is likely to aid conversion of nonerosive to erosive damage to the epithelium by permitting luminal acid greater access to the basolateral membrane of esophageal epithelial cells, which is known to be acid permeable.
authors.affiliation: Department of Medicine, Tulane University School of Medicine and the Veterans Administration Medical Center, New Orleans, Louisiana 70112, USA.
authors.forename: N A
authors.initials: NA
authors.lastname: Tobey
authors.forename: S S
authors.initials: SS
authors.lastname: Hosseini
authors.forename: C
authors.initials: C
authors.lastname: Caymaz-Bor
authors.forename: H R
authors.initials: HR
authors.lastname: Wyatt
authors.forename: G S
authors.initials: GS
authors.lastname: Orlando
authors.forename: R C
authors.initials: RC
authors.lastname: Orlando
mesh_terms: D000818:Animals; D004847:Epithelial Cells / Q000473:pathology; D004848:Epithelium / Q000473:pathology; D004947:Esophagus / Q000473:pathology*; D005744:Gastric Acid; D010434:Pepsin A / Q000502:physiology*; D011817:Rabbits
chemical_list: D010434:Pepsin A