Mechanisms of gastric juice-induced hyperpermeability of the cultured human tracheal epithelium.
OBJECTIVE
The respiratory aspiration of the stomach contents causes severe lung damage called aspiration pneumonia. The present study was undertaken to elucidate whether mucosal exposure of gastric juice causes hyperpermeability of the human airway epithelium and to determine the mechanisms responsible for gastric juice-induced airway epithelial damage.


METHODS
Gastric juice was collected from 46 normal adults via gastroscope and samples were analyzed for pH, osmolarity, and concentration of pepsin and trypsin. Tracheal surface epithelial cells were obtained from 16 autopsies, cultured onto porous filters, and mounted in the Ussing chamber. Electrical conductance (G) was measured before and after exposure of cells to gastric juice or Krebs-Henseleit solution with pH at 1.8, 2.8, 4.0, or 7.4 in the presence or absence of pepsin. D-[3H] mannitol flux study across the epithelial layer and histologic observations using an inverted microscope were also performed after exposure of cells to gastric juice.


RESULTS
Exposure of cultured human tracheal epithelium to gastric juice caused increases in G in a time- and pH-dependent fashion. A pepsin inhibitor (pepstatin A) inhibited gastric juice-induced increases in G at a pH of 2.8, and the addition of pepsin augmented increases in G induced by the Krebs-Henseleit solution at a pH of 1.8 and 2.8. Lowering the osmolarity of the solution to levels similar to gastric juice also potentiated increases in G induced by acid and pepsin. Gastric juice caused increases in D-[3H] mannitol flux across the epithelial layer bidirectionally, and microscopic observation revealed separation of the intercellular space and cell detachment from culture vessels after exposure of cells to gastric juice.


CONCLUSIONS
Gastric juice causes hyperpermeability across human airway epithelium probably through the additive effects of gastric acid, pepsin activity, and lower osmolarity.
Ohrui
T
T
Department of Geriatric Medicine, Tohoku University School of Medicine, Sendai, Japan.
Yamaya
M
M
Suzuki
T
T
Sekizawa
K
K
Funayama
T
T
Sekine
H
H
Sasaki
H
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002463:Cell Membrane Permeability / Q000502:physiology*; D002478:Cells, Cultured; D004848:Epithelium / Q000473:pathology / Q000502:physiology; D005750:Gastric Juice / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008875:Middle Aged; D009994:Osmolar Concentration; D010434:Pepsin A / Q000502:physiology; D014132:Trachea / Q000166:cytology / Q000502:physiology*
D010434:Pepsin A