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-adrenergic regulation of the eosinophil respiratory burst (as monitored with lucigenin-dependent luminescence) was evaluated. Normodense, nonprimed eosinophils from healthy volunteer subjects were potently inhibited by very low concentrations of isoproterenol. The inhibitory concentration of 50% for isoproterenol was approximately 2 nmol/L. The beta-agonist was able to inhibit the eosinophil respiratory burst induced by receptor-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 linkage. To determine whether cyclic adenosine 3',5' monophosphate (cAMP) may mediate beta-agonist effects, studies were performed with the type IV cAMP phosphodiesterase inhibitor Ro-201724. beta-Agonist inhibition 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 mediated by cAMP. Because regulation of the eosinophil by isoproterenol was observed at very low concentrations, these results may be relevant to pharmacologic effects of beta-agonists in disease states complicated by eosinophil activation during asthma.
Hadjokas
N E
NE
Research Unit, Veterans Affairs Medical Center, Boise, ID 83702.
Crowley
J J
JJ
Bayer
C R
CR
Nielson
C P
CP
D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D000166:Acridines; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000242:Cyclic AMP / Q000037:antagonists & inhibitors; D004804:Eosinophils / Q000502:physiology*; D006801:Humans; D008163:Luminescent Measurements; D009240:N-Formylmethionine Leucyl-Phenylalanine; D016897:Respiratory Burst / Q000187:drug effects*
D000166:Acridines; D000318:Adrenergic beta-Agonists; C033472:10,10'-dimethyl-9,9'-biacridinium; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D009240:N-Formylmethionine Leucyl-Phenylalanine; D000242:Cyclic AMP