Epithelial modulation of leukotriene-C4-induced human tracheal smooth muscle contraction

We investigated the role of epithelium in smooth muscle contraction induced by leukotriene C4 (LTC4) in isolated human trachea. The contractile response to LTC4 was potentiated by a gamma-glutamyl transpeptidase (gamma-GTP) inhibitor L-serine borate and by removal of the epithelium. Both L-serine borate (4.5 x 10(-2) M) and removal of the epithelium shifted the concentration-response curves to LTC4 to lower concentrations by 1.2 and 1.0 log units, respectively. Incubation of cultured human tracheal epithelial cells with either LTC4 or LTD4 resulted in the formation of LTD4 or LTE4. The isolated epithelial cells and cultured epithelial cells contained gamma-GTP activity. Histochemical study indicated that gamma-GTP-like activity was present in the epithelial, submucosal, and smooth muscle layers. These findings suggest that the epithelium modulates the contractile response to LTC4 in human trachea by LT-degrading enzymes.