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Intestinal Disease Research Program and Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
Ag challenge to the apical surface of tracheal epithelium results
in a rapid ion secretory response due to the activation of mast cells.
The aim of this study was to examine the impact of sensitization and
specific Ag challenge on the timing, route, and quantity of Ag
transported across tracheal epithelium. After sensitization of rats to
a model protein, HRP, tracheal tissues were excised and mounted in
Ussing chambers. Tracheas from HRP-sensitized rats, but not naive or
OVA-sensitized rats, responded to apical HRP challenge with a rise in
short-circuit current (beginning at 
2 min). Photomicrographs of
tissues fixed at 2 min showed that initial transepithelial HRP
transport occurred via endosomes and was significantly enhanced in
HRP-sensitized rats compared with both control groups. In addition,
nonciliated cells, the proportion of which increased after
sensitization, contained significantly more HRP than ciliated cells.
The hypersensitivity response occurred only in HRP-sensitized and
challenged rats and was associated with increased conductance of
tracheal epithelium and overall flux of HRP across the tissue. This
increased flux of Ag and elevated conductance was not observed in mast
cell-deficient Ws/Ws rats. Photomicrographs of tissues fixed 90 min
after challenge also showed HRP in the paracellular spaces between
adjacent epithelial cells. We conclude that sensitization increases
uptake of specific Ag initially via an endosomal transcellular pathway
across tracheal epithelium and that, after the hypersensitivity
reaction, mast cell-dependent recruitment of the paracellular pathway
further augments Ag influx into airway tissue.
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