MECHANISMS OF GASTRIC JUICE-INDUCED HYPERPERMEABILITY OF THE CULTUREDHUMAN TRACHEAL EPITHELIUM

Purpose: The respiratory aspiration of the stomach contents causes sev ere lung damage called aspiration pneumonia. The present study was und ertaken 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 dam age. Materials and 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 c ells were obtained from 16 autopsies, cultured onto porous filters, an d mounted in the Ussing chamber, Electrical conductance (G) was measur ed before and after exposure of cells to gastric juice or Krebs-Hensel eit solution with pH at 1.8, 2.8, 4.0, or 7.4 in the presence or absen ce of pepsin. D-[H-3] mannitol flux study across the epithelial layer and histologic observations using an inverted microscope were also per formed after exposure of cells to gastric juice. Results: Exposure of cultured human tracheal epithelium to gastric juice caused increases i n 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 incre ases in G induced by acid and pepsin. Gastric juice caused increases i n D-[H-3] mannitol flux across the epithelial layer bidirectionally, a nd microscopic observation revealed separation of the intercellular sp ace and cell detachment from culture vessels after exposure of cells t o gastric juice. Conclusion: Gastric juice causes hyperpemeability acr oss human airway epithelium probably through the additive effects of g astric acid, pepsin activity, and lower osmolarity.