Effects of extracellular pH on restitution and proliferation of rabbit oesophageal epithelial cells

Background and Aims: Exposure to luminal acid induces mucosal damage in the oesophagus. The extent and degree of interaction of acid with wound repair mechanisms of the oesophagus have not been explored, Methods: Rabbit oesophageal cells were isolated, cultured and exposed to di fferent extracellular pHs for several periods of time. Cell mortality was s tudied in both isolated and primary cultures of these cells by cell flow cy tometry using fluorochrome propidium iodide and LDH release, Subconfluent c ell cultures were used to study proliferative responses determined by [H-3] -thymidine incorporation into DNA, Restitution was studied in confluent mon olayers wounded by mechanical denudation. Results: Isolated cells were resistant to acid when exposed to pH > 2 for 1 5 min. Cell proliferation increased with small pH decreases (7-6.5) if the period of exposure was less than 6 h, but was inhibited with lower pHs and/ or longer periods of acid exposure, However, restitution was gradually inhi bited with further pH decreases (6.5-3) and time of acid exposure (0.5-24 h ). Conclusions: The wound repair activities of oesophageal epithelial cells ar e deeply affected by even small decreases in pH, These findings may help to explain the need for profound acid inhibition in acid-related reflux oesop hagitis.