Beta adrenergic modulation of formyl-methionine-leucine-phenylalanine-stimulated secretion of eosinophil peroxidase and leukotriene C4
Munoz, N.M.; Vita, A.J.; Neeley, S.P.; McAllister, K.; Spaethe, S.M.; White, S.R.; Leff, A.R.
Journal of Pharmacology and Experimental Therapeutics 268(1): 139-143
1994
ISSN/ISBN: 0022-3565 PMID: 8301549 Document Number: 424274
The inhibitory effect of beta-2 adrenergic receptor stimulation on leukotriene C-4 (LTC-4) secretion and eosinophil peroxidase (EPO) release caused by exogenous activation with 10-8 to 10-6 M formyl-met-leu-phe (fMLP) + 5 mu-g/ml of cytochalasin B (Cyto B) in purified human peripheral blood eosinophils was studied. Cells from normal subjects were isolated by negative immunoselection and remained gtoreq 98% viable as determined by trypan blue exclusion. Duplicate aliquots of eosinophils (10-5 cells/intervention) were activated with 1) fMLP + Cyto B alone, 2) fMLP + Cyto B after pretreatment with 10-8 M albuterol, 3) 10-8 M albuterol + fMLP + Cyto B after pretreatment with 10-8 M propranolol or 4) vehicle control. After incubation, the supernatants were tested for concentration of LTC-4 and EPO. Concentration-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 greatest 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 lt .02). Similarly, maximum EPO release increased from 277 +- 17.8 to 3956 +- 1230 ng/l 10-6 cells (P lt .02) after activation with fMLP + Cyto B. Treatment with albuterol decreased markedly both LTC-4 secretion to 144 +- 54.0 pg/ml (P lt .05 vs. fM LP + Cyto B-activated eosinophils) and EPO release to 1993 +- 368 ng/10-6 cells (P lt .05 vs. fM LP + Cyto B-activated eosinophils). Inhibition of LTC4 secretion caused by 10-8 M albuterol was reversed completely with 10-8 M propranolol (302 +- 70.8 pg/ml). Comparable reversal of inhibition of EPO secretion also was observed after treatment with propranolol. We demonstrate that direct beta adrenoceptor stimulation significantly decreased LTC-4 secretion and EPO release in fMLP + Cyto B-activated eosinophils and that this effect is reversed completely by propranolol. These findings suggest that the modulation of eosinophilic inflammation could result directly from beta adrenoceptor stimulation.