EOSINOPHILS AND NEUTROPHILS MODIFY ARACHIDONIC ACID-INDUCED RELAXATION OF GUINEA-PIG TRACHEA

The influence of inflammatory cells on airway reactivity was investiga ted on arachidonic acid-induced relaxations of guinea-pig trachea and on arachidonic acid metabolism in guinea-pig tracheal epithelial cells . The presence of either eosinophils or neutrophils (1.0 x 10(7) cells /ml), from bronchoalveolar lavage, decreased the tracheal relaxations induced by arachidonic acid (1.0-30 mu M). The basal synthesis of pros taglandin E(2) was increased in epithelial cells (from 176 +/- 36 to 7 920 +/- 898 pg/ml), eosinophils (from 360 +/- 56 to 2693 +/- 686 pg/ml ) and neutrophils (from 352 +/- 81 to 4400 +/- 272 pg/ml) following in cubation with arachidonic acid (10 mu M) The co-incubation of either e osinophils or neutrophils with epithelial cells, in the presence of ar achidonic acid, decreased the synthesis of prostaglandin E(3) (2600 +/ - 686 and 4400 +/- 272 pg/ml respectively) but increased the synthesis of thromboxane B-2 (from 60 +/- 6 to 11634 +/- 840 and 9282 +/- 485 p g/ml respectively). Similarly, when major basic protein-treated (100 m u g/ml) epithelial cells were incubated with arachidonic acid, the pro staglandin E(2) synthesis decreased (75%) but thromboxane B-2 synthesi s was unaffected. The results suggest that eosinophils and neutrophils may impair arachidonic acid metabolism in guinea-pig epithelium in fa vor of production of bronchoconstrictor prostanoids.