In:
Mediators of Inflammation, Hindawi Limited, Vol. 2014 ( 2014), p. 1-9
Abstract:
The clinical relevance of the anti-inflammatory properties of beta-2 agonists remains contentious possibly due to differences in their molecular structures and agonist activities. The current study has compared the effects of 3 different categories of β 2-agonists, namely, salbutamol (short-acting), formoterol (long-acting) and indacaterol (ultra-long-acting), at concentrations of 1–1000 nM, with human blood neutrophils in vitro . Neutrophils were activated with either N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP, 1 µM) or platelet-activating factor (PAF, 200 nM) in the absence and presence of the β 2-agonists followed by measurement of the generation of reactive oxygen species and leukotriene B4, release of elastase, and expression of the β 2-integrin, CR3, using a combination of chemiluminescence, ELISA, colorimetric, and flow cytometric procedures respectively. These were correlated with alterations in the concentrations of intracellular cyclic-AMP and cytosolic Ca 2+ . At the concentrations tested, formoterol and indacaterol caused equivalent, significant ( P 〈 0.05 at 1–10 nM) dose-related inhibition of all of the pro-inflammatory activities tested, while salbutamol was much less effective ( P 〈 0.05 at 100 nM and higher). Suppression of neutrophil reactivity was accompanied by elevations in intracellular cAMP and accelerated clearance of Ca 2+ from the cytosol of activated neutrophils. These findings demonstrate that β 2-agonists vary with respect to their suppressive effects on activated neutrophils.
Type of Medium:
Online Resource
ISSN:
0962-9351
,
1466-1861
Language:
English
Publisher:
Hindawi Limited
Publication Date:
2014
detail.hit.zdb_id:
2008065-7
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