Mast cell activation is involved in stress-induced epithelial barrier dysfunction in the esophagus.

Abstract

We aimed to investigate the role of mast cell in stress-induced barrier dysfunction in the esophagus and its possible pathway involved using mast cell-deficient (Ws/Ws) rats. Ws/Ws rats and normal (+/+) rats were submitted to chronic restraint stress (CRS) 2 h/day for 7 days. Tissues were obtained from distal esophagus. Mast cells were counted under Alcian blue-safranin O stain. Activation of mast cells was assessed using transmission electron microscope. Esophageal epithelial barrier dysfunction was evaluated by measuring intercellular spaces (ICS) and by quantifying tight junction (TJ) proteins. The localization and expression of mast cell-derived tryptase and proteinase activated receptor 2 (PAR-2) were assessed. A higher number of mast cells and higher proportion of activated mast cells were observed in CRS +/+ rats compared with non-stress controls. Increased ICS and decreased expression of some TJ proteins were observed in the CRS +/+ rats but not in the CRS Ws/Ws rats. Tryptase and its receptor PAR-2 were found elevated concomitantly by nearly 100% in CRS +/+ rats, but not in CRS Ws/Ws rats. Mast cells play an important role in stress-induced epithelial barrier dysfunction in esophagus. The mechanism may involve the activation of PAR-2 by mast cell-derived tryptase, causing proinflammatory responses and the subsequent disruption of the epithelial TJ proteins and a disturbed cytoskeleton function, resulting in dilated intercellular spaces.