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.