BETA-ADRENERGIC REGULATION OF THE EOSINOPHIL RESPIRATORY BURST AS DETECTED BY LUCIGENIN-DEPENDENT LUMINESCENCE

Because beta-adrenoceptor agonists are commonly used in the treatment of disease states associated with eosinophil activation, beta-adrenerg ic regulation of the eosinophil respiratory burst (as monitored with l ucigenin-dependent luminescence) was evaluated. Normodense, nonprimed eosinophils from healthy volunteer subjects were potently inhibited by very low concentrations of isoproterenol. The inhibitory concentratio n of 50% for isoproterenol was approximately 2 nmol/L. The beta-agonis t was able to inhibit the eosinophil respiratory burst induced by rece ptor-mediated (chemotactic peptide) and nonreceptor-mediated (calcium ionophore and phorbol ester) stimuli. Thus beta-agonist inhibition was unlikely to be isolated to an effect at the receptor or G protein lin kage. To determine whether cyclic adenosine 3',5' monophosphate (cAMP) may mediate beta-agonist effects, studies were performed with the typ e IV cAMP phosphodiesterase inhibitor Ro-201724. beta-agonist inhibiti on of the respiratory burst was clearly synergistic with effects of Ro -201724. We conclude that beta-adrenoceptor agonists can regulate the eosinophil respiratory burst at least partially through an effect medi ated by cAMP. Because regulation of the eosinophil by isoproterenol wa s observed at very low concentrations, these results may be relevant t o pharmacologic effects of beta-agonists in diseases states complicate d by eosinophil activation during asthma.