Dipeptidase inhibitor and epithelial removal potentiate leukotriene D4-induced human tracheal smooth muscle contraction.

We investigated the role of epithelium in smooth muscle contraction induced by leukotriene D4 (LTD4) in isolated human trachea. The contractile response to LTD4 was potentiated by an inhibitor of dipeptidases L-cysteine and by removal of the epithelium. Both L-cysteine (3 x 10(-3) M) and removal of the epithelium shifted the concentration-response curves to LTD4, to lower concentrations by 0.7 and 0.6 log units, respectively. Incubation of cultured or isolated human tracheal epithelial cells with LTD4 resulted in the formation of LTE4, which was completely blocked by pretreatment with L-cysteine (3 x 10(-3) M). The isolated and cultured human tracheal epithelial cells contained microsomal dipeptidase (MDP) activity. Immunohistochemical study indicated MDP protein was present in the epithelium and endothelial cells of submucosal microvessels in the human trachea. These results suggest that the epithelium modulates the contractile response to LTD4 in human trachea by dipeptidases degrading LTD4.