Beta adrenergic modulation of formyl-methionine-leucine-phenylalanine-stimulated secretion of eosinophil peroxidase and leukotriene C4.
The inhibitory effect of beta-2 adrenergic receptor stimulation on leukotriene C4 (LTC4) secretion and eosinophil peroxidase (EPO) release caused by exogenous activation with 10(-8) to 10(-6) M formyl-met-leu-phe (fMLP) + 5 micrograms/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 > or = 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 LTC4 and EPO. Concentration-related release of EPO was demonstrated for 10(-8) M fMLP + 5 micrograms/ml of Cyto B to 10(-6) M fMLP + 5 micrograms/ml of Cyto B, and the greatest concentration of fMLP was used in all subsequent studies. FMLP + Cyto B caused substantial LTC4 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 LTC4 secretion to 144 +/- 54.0 pg/ml (P < .05 vs. fMLP + Cyto B-activated eosinophils) and EPO release to 1993 +/- 368 ng/10(6) cells (P < .05 vs. fMLP + Cyto B-activated eosinophils).(ABSTRACT TRUNCATED AT 250 WORDS)
Munoz
N M
NM
Department of Medicine, University of Chicago, Illinois.
Vita
A J
AJ
Neeley
S P
SP
McAllister
K
K
Spaethe
S M
SM
White
S R
SR
Leff
A R
AR
D000420:Albuterol / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D017997:Leukotriene C4 / Q000378:metabolism*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D010544:Peroxidases / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects* / Q000378:metabolism
D018343:Receptors, Adrenergic, beta-2; D017997:Leukotriene C4; D003571:Cytochalasin B; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011433:Propranolol; D010544:Peroxidases; D000420:Albuterol