THE EFFECT OF 15-HPETE ON AIRWAY RESPONSIVENESS AND PULMONARY CELL RECRUITMENT IN RABBITS

1 In the present study we have investigated the effect of 15-hydropero xyeicosatetraenoic acid (15-HPETE) and 15-hydroxyeicosatetraenoic acid (15-HETE) on airway responsiveness to inhaled histamine in rabbits in vivo. 2 15-HPETE increased airway responsiveness to histamine 24 h af ter tracheal instillation and this was associated with a cellular infi ltration consisting mainly of neutrophils, as measured by bronchoalveo lar lavage. The airway hyperresponsiveness induced by 15-HPETE was sti ll present 72 h after tracheal instillation of 15-HPETE, but had retur ned to baseline values one week post challenge. The number of neutroph ils in bronchoalveolar lavage remained significantly elevated compared to pre-challenge levels. In contrast to 15-HPETE, the major metabolit e 15-HETE, failed to alter airway hyperresponsiveness to histamine des pite the recruitment of neutrophils into the lung, suggesting that the effect of 15-HPETE was not secondary to the generation of this metabo lite nor dependent on the influx of neutrophils. 3 Both capsaicin and atropine but not the peripherally acting mu-opioid receptor agonist, B W443C (H-Tyr-D-Arg-Gly-Phe(4-NO2) -Pro-NH4), attenuated 15-HPETE-induc ed hyperresponsiveness. The increased cellular infiltration induced by 15-HPETE was only attenuated by capsaicin. 4 The results of the prese nt study suggest that the release of 15-HPETE into the airways could c ontribute to sensitization of afferent nerve endings analogous to the hyperalgesia induced by this mediator in skin.