Paradoxical blockade of beta adrenergically mediated inhibition of stimulated eosinophil secretion by salmeterol.
Salmeterol (SALM) is a long-acting beta 2 adrenoceptor agonist that causes prolonged relaxation of airway smooth muscle. To determine whether this agent also causes prolonged inhibition of stimulated eosinophil secretion, we studied interactions between SALM and albuterol (ALB) in inhibiting eosinophil peroxidase (EPO) secretion in human eosinophils in vitro. Peripheral blood eosinophils were isolated from 18 human volunteers by negative immunoselection, and secretion of EPO was elicited with 10(-6) M formyl-met-leu-phe (fMLP) + 5 micrograms/ml cytochalasin B (CytB) in aliquots of 10(5) cells. Eosinophils were pretreated with either 10(-8) M ALB, 10(-8) M SALM or SALM + ALB for 5 min to 18 hr at 37 degrees C. Pretreatment with ALB for 5 min caused inhibition of stimulated secretion of EPO to 783 +/- 210 ng/10(6) cells vs. 1475 +/- 286 ng/10(6) cells for eosinophils not treated with ALB (P < .05; n = 5). Inhibition of EPO secretion caused by ALB was sustained for 30 min (924 +/- 160 ng/10(6) cells; P < .05 vs. fMLP + CytB; n = 5). By contrast, SALM had no inhibitory effect on fMLP-induced secretion after incubation for 5 min to 18 hr. In cells obtained from four separate isolations, pretreatment with 10(-8)M SALM before addition of ALB blocked the inhibition of EPO release caused by 10(-8)M ALB alone (486 +/- 28 ng/10(6) cells for ALB alone vs. 902 +/- 32 ng/10(6) cells for SALM + ALB; P < .01; n = 4).(ABSTRACT TRUNCATED AT 250 WORDS)
Muñoz
N M
NM
Department of Medicine, University of Chicago, Illinois, USA.
Rabe
K F
KF
Vita
A J
AJ
McAllister
K
K
Mayer
D
D
Weiss
M
M
Leff
A R
AR
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D047209:Eosinophil Peroxidase; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D010544:Peroxidases / Q000378:metabolism; D000068299:Salmeterol Xinafoate
D000318:Adrenergic beta-Agonists; D000068299:Salmeterol Xinafoate; D000242:Cyclic AMP; D047209:Eosinophil Peroxidase; D010544:Peroxidases; D000420:Albuterol