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Differential effects of short-acting beta2-agonists on human granulocyte functions.

Abstract：

BACKGROUND:beta2-Adrenergic agonists play a pivotal role in the management of bronchial asthma. Although the major effect of short-acting beta2-agonists on the airway is relaxation of smooth muscles, they may also have several effects on surrounding immunomodulatory cells. METHODS:We examined whether widely used short-acting beta2-agonists differ in their ability to modulate granulocyte functions, such as superoxide anion (O2-) production and degranulation. RESULTS:Procaterol (PC), a full agonist, significantly inhibited both O2- production by granulocytes (neutrophils and eosinophils) and their degranulation at the clinically relevant concentrations, whereas salbutamol and tulobuterol (partial agonists) showed smaller effects. PC inhibited N-formyl methionyl-leucyl-phenylalanine-induced O2- production and peroxidase release, but failed to inhibit responses induced by phorbol 12-myristate 13-acetate and/or opsonized zymosan. Exposure to 5 x 10(-8)M PC for 120 min resulted in approximately 50% inhibition of O2- production and degranulation of neutrophils. The effects of beta2-agonists were more obvious in neutrophils than in eosinophils. A selective beta2-receptor antagonist, ICI-118551, reversed the inhibitory effect of beta2-agonists (PC, salbutamol, tulobuterol B) on N-formyl methionyl-leucyl-phenylalanine-induced O2- production. CONCLUSIONS:These results suggest that beta2-agonists had an inhibitory effect on granulocyte functions, mainly mediated viareceptors and their efficacy. Our observations support that beta2-agonists with a rapid onset of action and high intrinsic efficacy (short-acting and full agonists) may be optimal for the rescue therapy against acute asthma attack and sedation of its airway inflammation in an early phase.

journal_name

Int Arch Allergy Immunol

journal_title

International archives of allergy and immunology

authors

Yasui K,Kobayashi N,Yamazaki T,Agematsu K,Matsuzaki S,Nakata S,Baba A

doi

10.1159/000089516

keywords:

subject

Has Abstract

pub_date

2006-01-01 00:00:00

pages

1-8

issue

1

eissn

1018-2438

issn

1423-0097

pii

89516

journal_volume

139

pub_type

杂志文章

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