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A Reversible, Non-invasive Method for Airway Resistance Measurements and Bronchoalveolar Lavage Fluid Sampling in Mice
Published on: April 13, 2010
Correlation between blood eosinophilia and airways hyper-responsiveness in rats
B A Spicer1, R Baker, S M Laycock
1Beecham Pharmaceuticals Research Division, Epsom, Surrey, UK.
Summary
Intravenous Sephadex particle injection in rats induced blood eosinophilia and heightened airway reactivity to 5-hydroxytryptamine (5-HT). This eosinophilia correlated with increased sensitivity to 5-HT effects, both in vivo and in vitro.
Area of Science:
- Pharmacology
- Immunology
- Respiratory Physiology
Background:
- 5-hydroxytryptamine (5-HT) is a potent mediator of airway smooth muscle contraction.
- Eosinophils are implicated in allergic airway inflammation and hyperresponsiveness.
Purpose of the Study:
- To investigate the effect of Sephadex particle injection on airway responsiveness to 5-HT in rats.
- To determine the relationship between blood eosinophil levels and airway hyperresponsiveness.
Main Methods:
- Intravenous administration of Sephadex particles to rats.
- Assessment of in vivo respiratory responses to 5-HT.
- Measurement of in vitro lung strip reactivity to 5-HT.
- Quantification of blood eosinophil counts.
Main Results:
- Sephadex injection caused significant blood eosinophilia in rats.
- Rats treated with Sephadex exhibited enhanced in vivo sensitivity to 5-HT's respiratory effects.
- In vitro lung strips from Sephadex-treated rats showed increased reactivity (greater slope and maximal response) to 5-HT.
- Both in vivo hyper-sensitivity and in vitro hyper-reactivity correlated with elevated blood eosinophil levels.
Conclusions:
- Sephadex-induced eosinophilia is associated with augmented airway responsiveness to 5-HT.
- Eosinophils may play a role in modulating airway reactivity to serotonergic stimuli.
- This model provides insights into mechanisms underlying airway hyperresponsiveness.
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