Enhanced antigen transport across eat tracheal epithelium induced by sensitization and mast cell activation

Ag challenge to the apical surface of tracheal epithelium results in a rapi d ion secretory response due to the activation of mast cells. The aim of th is study was to examine the impact of sensitization and specific Ag challen ge on the timing, route, and quantity of Ag transported across tracheal epi thelium. After sensitization of rats to a model protein, HRP, tracheal tiss ues were excised and mounted in Ussing chambers. Tracheas from HRP-sensitiz ed rats, but not naive or OVA-sensitized rats, responded to apical HRP chal lenge with a rise in short-circuit current (beginning; at similar to 2 min) . Photomicrographs of tissues fixed at 2 min showed that initial transepith elial HRP transport occurred via endosomes and was significantly enhanced i n HRP-sensitized rats compared with both control groups. In addition, nonci liated cells, the proportion of which increased after sensitization, contai ned significantly more HRP than ciliated cells. The hypersensitivity respon se occurred only in HRP-sensitized and challenged rats and was associated w ith increased conductance of tracheal epithelium and overall flux of HRP ac ross the tissue. This increased flux of Ag and elevated conductance was not observed in mast cell-deficient Ws/Ws rats. Photomicrographs of tissues fi xed 90 min after challenge also showed HRP in the paracellular spaces betwe en adjacent epithelial cells. We conclude that sensitization increases upta ke of specific Ag initially via an endosomal transcellular pathway across t racheal epithelium and that, after the hypersensitivity reaction, mast cell -dependent recruitment of the paracellular pathway further augments Ag infl ux into airway tissue.