Inhibitory effects of formoterol on platelet-activating factor induced eosinophil chemotaxis and degranulation.
A new long-acting beta 2-agonist, formoterol, has been reported to have a greater efficacy and duration of action in asthmatic patients as compared to conventional beta 2-agonists. We recently demonstrated that formoterol inhibited antigen-induced late asthmatic response (LAR) and accompanying airway eosinophilia in guinea pigs. In this study, we investigated the direct effect of formoterol in vitro on human eosinophil function, focusing on platelet-activating factor (PAF)-induced eosinophil chemotaxis and eosinophil cationic protein (ECP) release. Purified normodense eosinophils were separated by discontinuous gradient from 12 mild asthmatic patients. Formoterol in concentrations of 1-100 microM significantly inhibited PAF-induced eosinophil chemotaxis in a dose-dependent manner with a concentration of drug required to produce 50% inhibition (IC50) of 10.16 microM; % inhibition: 22.9 +/- 13.0% (1 microM), 51.6 +/- 12.7% (10 microM), 75.0 +/- 11.3% (100 microM). When formyl-methionyl-leucyl-phenylamine (FMLP) was used as a chemoattractant, a similar inhibition of eosinophil chemotaxis by formoterol was observed; % inhibition: 13.1 +/- 5.0% (1 microM). 47.7 +/- 7.6% (10 microM), 65.5 +/- 16.5% (100 microM). A conventional beta 2-agonist, salbutamol, at doses to 100 microM did not show any inhibitory effects on PAF-induced eosinophil chemotaxis. Formoterol in concentrations of 1-100 microM also significantly inhibited PAF-induced ECP release from eosinophils; % inhibition: 21.7 +/- 9.0% (1 microM), 39.3 +/- 7.4% (10 microM), 39.6 +/- 8.4% (100 microM). In the presence of phosphodiesterase inhibitors, theophylline or isobutylmethyl xanthine (IBMX), the inhibition by formoterol on PAF-induced ECP release was enhanced.(ABSTRACT TRUNCATED AT 250 WORDS)
Eda
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R
Allergic Disease Center, Creighton University, School of Medicine, Omaha, Nebr. 68178.
Sugiyama
H
H
Hopp
R J
RJ
Okada
C
C
Bewtra
A K
AK
Townley
R G
RG
D000328:Adult; D000420:Albuterol / Q000494:pharmacology; D001249:Asthma / Q000276:immunology; D001798:Blood Proteins / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology*; D004983:Ethanolamines / Q000494:pharmacology*; D005260:Female; D000068759:Formoterol Fumarate; D006801:Humans; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000276:immunology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000276:immunology; D011433:Propranolol / Q000494:pharmacology; D012260:Ribonucleases
D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D004983:Ethanolamines; D010972:Platelet Activating Factor; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011433:Propranolol; D012260:Ribonucleases; D000420:Albuterol; D000068759:Formoterol Fumarate