BETA-ADRENERGIC MODULATION OF FORMYL-METHIONINE-LEUCINE-PHENYLALANINE-STIMULATED SECRETION OF EOSINOPHIL PEROXIDASE AND LEUKOTRIENE C-4

The inhibitory effect of beta-2 adrenergic receptor stimulation on leu kotriene C-4 (LTC(4)) secretion and eosinophil peroxidase (EPO) releas e caused by exogenous activation with 10(-8) to 10(-6) M formyl-met-le u-phe (fMLP) + 5 mu g/ml of cytochalasin B (Cyto B) in purified human peripheral blood eosinophils was studied. Cells from normal subjects w ere isolated by negative immunoselection and remained greater than or equal to 98% viable as determined by trypan blue exclusion. Duplicate aliquots of eosinophils (10(5) cells/intervention) were activated with I)fMLP + Cyto B alone, 2) fMLP + Cyto B after pretreatment with 10(-8 ) M albuterol, 3) 10(-8) M albuterol + fMLP + Cyto B after pretreatmen t with 10(-8) M propranolol or 4) vehicle control. After incubation, t he supernatants were tested for concentration of LTC(4) and EPO. Conce ntration-related release of EPO was demonstrated for 10(-8) M fMLP + 5 mu g/ml of Cyto B to 10(-6) M fMLP + 5 mu g/ml of Cyto B, and the gre atest concentration of fMLP was used in all subsequent studies. FMLP Cyto B caused substantial LTC(4) secretion in eosinophils (300 +/- 83 .0 pg/ml) as compared to sham-activated eosinophils (3.3 +/- 1.9 pg/ml ; P <.02). Similarly, maximum EPO release increased from 277 +/- 17.8 to 3956 +/- 1230 ng/10(6) cells (P <.02) after activation with fMLP Cyto B. Treatment with albuterol decreased markedly both LTC(4) secret ion to 144 +/- 54.0 pg/ml (P <.05 vs, fMLP + Cyto B-activated eosinoph ils) and EPO release to 1993 +/- 368 ng/10(6) cells (P <.05 vs. fMLP Cyto B-activated eosinophils). Inhibition of LTC(4) secretion caused by 10(-8) M albuterol was reversed completely with 10(-8) M propranolo l (302 +/- 70.8 pg/ml). Comparable reversal of inhibition of EPO secre tion also was observed after treatment with propranolol. We demonstrat e that direct beta adrenoceptor stimulation significantly decreased LT C(4) secretion and EPO release in fMLP + Cyto B-activated eosinophils and that this effect is reversed completely by propranolol. These find ings suggest that the modulation of eosinophilic inflammation could re sult directly from beta adrenoceptor stimulation.