ENDOTHELIN-1 INDUCES STIMULATION OF PROSTAGLANDIN SYNTHESIS IN CELLS OBTAINED FROM CANINE AIRWAYS BY BRONCHOALVEOLAR LAVAGE

Endothelin-1 (ET-1), a potent mediator released by airway epithelial cells, Often exerts its effects in the lung through stimulation of arachidonic acid (AA) metabolism. To investigate its range of influence, we studied the action of ET-1 on the synthesis and release of thromboxane (TX)B2, prostaglandin (PG)D2, and histamine from canine airway cells obtained by bronchoalveolar lavage (BAL). ET-1 (10(-10), 10(-9) and 10(-8)M) stimulated production of TXB2 and PGD2 by BAL cell preparations in a dose-related manner in the absence of measurable histamine release. Release of TXB2 was 10-fold higher than that of PGD2. The effect of ET-1 on AA metabolism in alveolar macrophages was evaluated in preparations of purified (> 99%) cells labelled for 20-22 hrs with H-3-AA prior to stimulation. ET-1 (10(-8),10(-7), 10(-6)M) induced significant, dose-related release of H-3-AA and its metabolites from alveolar macrophages, to levels 350% above control. These studies indicate that low levels of ET-1 can stimulate AA metabolism in resident luminal airway cells, including alveolar macrophages, and suggest that the function of these luminal cells may be modulated by the epithelium, in vivo, through the release of this peptide into the airways.