EPITHELIAL MODULATION OF LEUKOTRIENE-C-4-INDUCED HUMAN TRACHEAL SMOOTH-MUSCLE CONTRACTION

We investigated the role of epithelium in smooth muscle contraction in duced by leukotriene C-4 (LTC(4)) in isolated human trachea. The contr actile response to LTC(4) was potentiated by a gamma-glutamyl transpep tidase (gamma-GTP) inhibitor L-serine berate and by removal of the epi thelium. Both L-serine berate (4.5 x 10(-2) M) and removal of the epit helium shifted the concentration-response curves to LTC(4) to lower co ncentrations by 1.2 and 1.0 log units, respectively. Incubation of cul tured human tracheal epithelial cells with either LTC(4) or LTD(4) res ulted in the formation of LTD(4) or LTE(4). The isolated epithelial ce lls and cultured epithelial cells contained gamma-GTP activity. Histoc hemical study indicated that gamma-GTP-like activity was present in th e epithelial, submucosal, and smooth muscle layers. These findings sug gest that the epithelium modulates the contractile response to LTC(4) in human trachea by LT-degrading enzymes.