Inhibitory effects of formoteroi on platelet-activating factor induced eosinophil chemotaxis and degranulation

Ryosuke Eda, Haruhito Sugiyama, Russell J. Hupp, Chiharu Okada, Againdra K. Bewtra, Robert G. Townley

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

A new long-acting β2-agonist, formoteroi, has been reported to have a greater efficacy and duration of action in asthmatic patients as compared to conventional (β2-agonists. We recently demonstrated that formoteroi inhibited antigen-induced late asthmatic response (LAR) and accompanying airway eosi- nophilia in guinea pigs. In this study, we investigated the direct effect of formoteroi 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. Formoteroi in concentrations of 1-100 μΜ 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 μΜ; % inhibition: 22.9±13.0% (1 μΜ). 51.6 ± 12.7% (10 μΜ), 75.0 ± 11.3% (100 μΜ). When formyl-methionyl-leueyl-phenylamine (FMLP) was used as a ehemoattractant, a similar inhibition of eosinophil chemotaxis by formoteroi was observed; % inhibition: 13.1 ± 5.0% (1 μΜ). 47.7 ±7.6% (10 μΜ). 65.5 ± 16.5% (100 μM). A conventional β2-agonist, salbutamol, at doses to 100 μΜ did not show any inhibitory effects on PAF-induced eosinophil chemotaxis. Formoteroi in concentrations of 1-100 μΜ also significantly inhibited PAF-induced ECP release from eosinophils; % inhibition: 21.7 ± 9.0% (1 μΜ), 39.3 ± 7.4% (10 μΜ), 39.6 ± 8.4% (100 μΜ).In the presence of phosphodiesterase inhibitors, theophylline or isobutylmethyl xanthine (IBMX), the inhibition by formoteroi on PAF-induced ECP release was enhanced. The combination of formoteroi (10 μΛ7) and IBMX (10 μΜ) achieved 70.3 ± 7.6% inhibition. Salbutamol in concentrations of 0.1 -100 μΜ failed to inhibit PAF-induced ECP release. The inhibition of PAF-induced eosinophil chemotaxis and ECP release by formoteroi were not abolished by propranolol. This comparison between formoteroi and salbutamol suggestes that formoteroi is not only a longer-acting β2-agonist but may have more beneficial properties to prevent eosinophil-mediated inflammatory processes of LAR than conventional β2-agonists.

Original languageEnglish
Pages (from-to)391-398
Number of pages8
JournalInternational Archives of Allergy and Immunology
Volume102
Issue number4
DOIs
StatePublished - 1993

Fingerprint

Platelet Activating Factor
Chemotaxis
Eosinophils
Eosinophil Cationic Protein
Albuterol
Xanthine
Aniline Compounds
Cell Migration Inhibition
Phosphodiesterase Inhibitors
Eosinophilia
Theophylline
Inhibition (Psychology)
Propranolol
Inhibitory Concentration 50
Guinea Pigs
Antigens

All Science Journal Classification (ASJC) codes

  • Immunology
  • Immunology and Allergy

Cite this

Inhibitory effects of formoteroi on platelet-activating factor induced eosinophil chemotaxis and degranulation. / Eda, Ryosuke; Sugiyama, Haruhito; Hupp, Russell J.; Okada, Chiharu; Bewtra, Againdra K.; Townley, Robert G.

In: International Archives of Allergy and Immunology, Vol. 102, No. 4, 1993, p. 391-398.

Research output: Contribution to journalArticle

Eda, Ryosuke ; Sugiyama, Haruhito ; Hupp, Russell J. ; Okada, Chiharu ; Bewtra, Againdra K. ; Townley, Robert G. / Inhibitory effects of formoteroi on platelet-activating factor induced eosinophil chemotaxis and degranulation. In: International Archives of Allergy and Immunology. 1993 ; Vol. 102, No. 4. pp. 391-398.
@article{6a8dc52fb85645f091907c5e3694c444,
title = "Inhibitory effects of formoteroi on platelet-activating factor induced eosinophil chemotaxis and degranulation",
abstract = "A new long-acting β2-agonist, formoteroi, has been reported to have a greater efficacy and duration of action in asthmatic patients as compared to conventional (β2-agonists. We recently demonstrated that formoteroi inhibited antigen-induced late asthmatic response (LAR) and accompanying airway eosi- nophilia in guinea pigs. In this study, we investigated the direct effect of formoteroi 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. Formoteroi in concentrations of 1-100 μΜ 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 μΜ; {\%} inhibition: 22.9±13.0{\%} (1 μΜ). 51.6 ± 12.7{\%} (10 μΜ), 75.0 ± 11.3{\%} (100 μΜ). When formyl-methionyl-leueyl-phenylamine (FMLP) was used as a ehemoattractant, a similar inhibition of eosinophil chemotaxis by formoteroi was observed; {\%} inhibition: 13.1 ± 5.0{\%} (1 μΜ). 47.7 ±7.6{\%} (10 μΜ). 65.5 ± 16.5{\%} (100 μM). A conventional β2-agonist, salbutamol, at doses to 100 μΜ did not show any inhibitory effects on PAF-induced eosinophil chemotaxis. Formoteroi in concentrations of 1-100 μΜ also significantly inhibited PAF-induced ECP release from eosinophils; {\%} inhibition: 21.7 ± 9.0{\%} (1 μΜ), 39.3 ± 7.4{\%} (10 μΜ), 39.6 ± 8.4{\%} (100 μΜ).In the presence of phosphodiesterase inhibitors, theophylline or isobutylmethyl xanthine (IBMX), the inhibition by formoteroi on PAF-induced ECP release was enhanced. The combination of formoteroi (10 μΛ7) and IBMX (10 μΜ) achieved 70.3 ± 7.6{\%} inhibition. Salbutamol in concentrations of 0.1 -100 μΜ failed to inhibit PAF-induced ECP release. The inhibition of PAF-induced eosinophil chemotaxis and ECP release by formoteroi were not abolished by propranolol. This comparison between formoteroi and salbutamol suggestes that formoteroi is not only a longer-acting β2-agonist but may have more beneficial properties to prevent eosinophil-mediated inflammatory processes of LAR than conventional β2-agonists.",
author = "Ryosuke Eda and Haruhito Sugiyama and Hupp, {Russell J.} and Chiharu Okada and Bewtra, {Againdra K.} and Townley, {Robert G.}",
year = "1993",
doi = "10.1159/000236588",
language = "English",
volume = "102",
pages = "391--398",
journal = "International Archives of Allergy and Immunology",
issn = "1018-2438",
publisher = "S. Karger AG",
number = "4",

}

TY - JOUR

T1 - Inhibitory effects of formoteroi on platelet-activating factor induced eosinophil chemotaxis and degranulation

AU - Eda, Ryosuke

AU - Sugiyama, Haruhito

AU - Hupp, Russell J.

AU - Okada, Chiharu

AU - Bewtra, Againdra K.

AU - Townley, Robert G.

PY - 1993

Y1 - 1993

N2 - A new long-acting β2-agonist, formoteroi, has been reported to have a greater efficacy and duration of action in asthmatic patients as compared to conventional (β2-agonists. We recently demonstrated that formoteroi inhibited antigen-induced late asthmatic response (LAR) and accompanying airway eosi- nophilia in guinea pigs. In this study, we investigated the direct effect of formoteroi 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. Formoteroi in concentrations of 1-100 μΜ 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 μΜ; % inhibition: 22.9±13.0% (1 μΜ). 51.6 ± 12.7% (10 μΜ), 75.0 ± 11.3% (100 μΜ). When formyl-methionyl-leueyl-phenylamine (FMLP) was used as a ehemoattractant, a similar inhibition of eosinophil chemotaxis by formoteroi was observed; % inhibition: 13.1 ± 5.0% (1 μΜ). 47.7 ±7.6% (10 μΜ). 65.5 ± 16.5% (100 μM). A conventional β2-agonist, salbutamol, at doses to 100 μΜ did not show any inhibitory effects on PAF-induced eosinophil chemotaxis. Formoteroi in concentrations of 1-100 μΜ also significantly inhibited PAF-induced ECP release from eosinophils; % inhibition: 21.7 ± 9.0% (1 μΜ), 39.3 ± 7.4% (10 μΜ), 39.6 ± 8.4% (100 μΜ).In the presence of phosphodiesterase inhibitors, theophylline or isobutylmethyl xanthine (IBMX), the inhibition by formoteroi on PAF-induced ECP release was enhanced. The combination of formoteroi (10 μΛ7) and IBMX (10 μΜ) achieved 70.3 ± 7.6% inhibition. Salbutamol in concentrations of 0.1 -100 μΜ failed to inhibit PAF-induced ECP release. The inhibition of PAF-induced eosinophil chemotaxis and ECP release by formoteroi were not abolished by propranolol. This comparison between formoteroi and salbutamol suggestes that formoteroi is not only a longer-acting β2-agonist but may have more beneficial properties to prevent eosinophil-mediated inflammatory processes of LAR than conventional β2-agonists.

AB - A new long-acting β2-agonist, formoteroi, has been reported to have a greater efficacy and duration of action in asthmatic patients as compared to conventional (β2-agonists. We recently demonstrated that formoteroi inhibited antigen-induced late asthmatic response (LAR) and accompanying airway eosi- nophilia in guinea pigs. In this study, we investigated the direct effect of formoteroi 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. Formoteroi in concentrations of 1-100 μΜ 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 μΜ; % inhibition: 22.9±13.0% (1 μΜ). 51.6 ± 12.7% (10 μΜ), 75.0 ± 11.3% (100 μΜ). When formyl-methionyl-leueyl-phenylamine (FMLP) was used as a ehemoattractant, a similar inhibition of eosinophil chemotaxis by formoteroi was observed; % inhibition: 13.1 ± 5.0% (1 μΜ). 47.7 ±7.6% (10 μΜ). 65.5 ± 16.5% (100 μM). A conventional β2-agonist, salbutamol, at doses to 100 μΜ did not show any inhibitory effects on PAF-induced eosinophil chemotaxis. Formoteroi in concentrations of 1-100 μΜ also significantly inhibited PAF-induced ECP release from eosinophils; % inhibition: 21.7 ± 9.0% (1 μΜ), 39.3 ± 7.4% (10 μΜ), 39.6 ± 8.4% (100 μΜ).In the presence of phosphodiesterase inhibitors, theophylline or isobutylmethyl xanthine (IBMX), the inhibition by formoteroi on PAF-induced ECP release was enhanced. The combination of formoteroi (10 μΛ7) and IBMX (10 μΜ) achieved 70.3 ± 7.6% inhibition. Salbutamol in concentrations of 0.1 -100 μΜ failed to inhibit PAF-induced ECP release. The inhibition of PAF-induced eosinophil chemotaxis and ECP release by formoteroi were not abolished by propranolol. This comparison between formoteroi and salbutamol suggestes that formoteroi is not only a longer-acting β2-agonist but may have more beneficial properties to prevent eosinophil-mediated inflammatory processes of LAR than conventional β2-agonists.

UR - http://www.scopus.com/inward/record.url?scp=0027433533&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027433533&partnerID=8YFLogxK

U2 - 10.1159/000236588

DO - 10.1159/000236588

M3 - Article

VL - 102

SP - 391

EP - 398

JO - International Archives of Allergy and Immunology

JF - International Archives of Allergy and Immunology

SN - 1018-2438

IS - 4

ER -