Fluvastatin and lovastatin inhibit granulocyte macrophage-colony stimulating factor-stimulated human eosinophil adhesion to inter-cellular adhesion molecule-1 under flow conditions

A. J. Robinson, D. Kashanin, F. O'Dowd, K. Fitzgerald, V. Williams, Garry Michael Walsh

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Background

Eosinophil accumulation in the lung is an important feature of airway inflammation in asthma. There is therefore much interest in developing novel therapies to prevent this process. Accumulating evidence suggests that statins have anti-inflammatory properties, including inhibition of leucocyte accumulation. We therefore assessed the ability of five statins to inhibit human eosinophil adhesion to recombinant human inter-cellular adhesion molecule (rhICAM)-1 under physiologically relevant flow conditions.

Methods

Purified eosinophils were pre-treated with a panel of statins before elucidation of the adhesion profiles of resting and granulocyte macrophage-colony stimulating factor (GM-CSF)-stimulated cells to rhICAM-1-coated microchannels at a flow rate of 0.5 dynes/cm2. Images were recorded in real-time at 1 min intervals and analysed using Ducocell software.

Results

Fluvastatin and lovastatin (both 10 nm) significantly inhibited GM-CSF-stimulated eosinophil adhesion to rhICAM-1 after 2 min (34.4 +/- 3.0% inhibition and 37.8 +/- 12.6% inhibition, respectively, n=4, P < 0.05) but had no significant inhibitory effect on unstimulated eosinophil adhesion. Mevastatin, simvastatin, and pravastatin (all 10 nm) had no significant effect on GM-CSF-stimulated eosinophil adhesion to rhICAM-1. A concentration range of fluvastatin and lovastatin inhibited GM-CSF stimulated eosinophil adhesion with significant (P < 0.05) inhibition observed at low concentrations of 1 nm for both drugs. Mevalonate (100 nm) reversed fluvastatin-mediated but not lovastatin-mediated inhibition of eosinophil adhesion.

Conclusions

Inhibition of eosinophil adhesion to ICAM-1 by fluvastatin and lovastatin under physiological shear stress represent novel actions by these drugs that may inform the development of anti-inflammatory therapy for allergic disease.

Cite this as: A. J. Robinson, D. Kashanin, F. O'Dowd, K. Fitzgerald, V. Williams and G. M. Walsh, Clinical & Experimental Allergy, 2009 (39) 1866-1874.

Original languageEnglish
Pages (from-to)1866-1874
Number of pages9
JournalClinical & experimental allergy
Volume39
Issue number12
Early online date18 Aug 2009
DOIs
Publication statusPublished - Dec 2009

Keywords

  • adhesion
  • asthma
  • eosinophils
  • fluvastatin
  • ICAM-1
  • lovastatin
  • statins
  • antiinflammatory properties
  • intercellular-adhesion
  • epithelial-cells
  • allergic-asthma
  • expression
  • simvastatin
  • inflammation
  • recruitment
  • pathway

Cite this

Fluvastatin and lovastatin inhibit granulocyte macrophage-colony stimulating factor-stimulated human eosinophil adhesion to inter-cellular adhesion molecule-1 under flow conditions. / Robinson, A. J.; Kashanin, D.; O'Dowd, F.; Fitzgerald, K.; Williams, V.; Walsh, Garry Michael.

In: Clinical & experimental allergy, Vol. 39, No. 12, 12.2009, p. 1866-1874.

Research output: Contribution to journalArticle

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title = "Fluvastatin and lovastatin inhibit granulocyte macrophage-colony stimulating factor-stimulated human eosinophil adhesion to inter-cellular adhesion molecule-1 under flow conditions",
abstract = "Background Eosinophil accumulation in the lung is an important feature of airway inflammation in asthma. There is therefore much interest in developing novel therapies to prevent this process. Accumulating evidence suggests that statins have anti-inflammatory properties, including inhibition of leucocyte accumulation. We therefore assessed the ability of five statins to inhibit human eosinophil adhesion to recombinant human inter-cellular adhesion molecule (rhICAM)-1 under physiologically relevant flow conditions. Methods Purified eosinophils were pre-treated with a panel of statins before elucidation of the adhesion profiles of resting and granulocyte macrophage-colony stimulating factor (GM-CSF)-stimulated cells to rhICAM-1-coated microchannels at a flow rate of 0.5 dynes/cm2. Images were recorded in real-time at 1 min intervals and analysed using Ducocell software. Results Fluvastatin and lovastatin (both 10 nm) significantly inhibited GM-CSF-stimulated eosinophil adhesion to rhICAM-1 after 2 min (34.4 +/- 3.0{\%} inhibition and 37.8 +/- 12.6{\%} inhibition, respectively, n=4, P < 0.05) but had no significant inhibitory effect on unstimulated eosinophil adhesion. Mevastatin, simvastatin, and pravastatin (all 10 nm) had no significant effect on GM-CSF-stimulated eosinophil adhesion to rhICAM-1. A concentration range of fluvastatin and lovastatin inhibited GM-CSF stimulated eosinophil adhesion with significant (P < 0.05) inhibition observed at low concentrations of 1 nm for both drugs. Mevalonate (100 nm) reversed fluvastatin-mediated but not lovastatin-mediated inhibition of eosinophil adhesion. Conclusions Inhibition of eosinophil adhesion to ICAM-1 by fluvastatin and lovastatin under physiological shear stress represent novel actions by these drugs that may inform the development of anti-inflammatory therapy for allergic disease. Cite this as: A. J. Robinson, D. Kashanin, F. O'Dowd, K. Fitzgerald, V. Williams and G. M. Walsh, Clinical & Experimental Allergy, 2009 (39) 1866-1874.",
keywords = "adhesion, asthma, eosinophils, fluvastatin, ICAM-1, lovastatin, statins, antiinflammatory properties, intercellular-adhesion , epithelial-cells, allergic-asthma, expression, simvastatin, inflammation, recruitment, pathway",
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T1 - Fluvastatin and lovastatin inhibit granulocyte macrophage-colony stimulating factor-stimulated human eosinophil adhesion to inter-cellular adhesion molecule-1 under flow conditions

AU - Robinson, A. J.

AU - Kashanin, D.

AU - O'Dowd, F.

AU - Fitzgerald, K.

AU - Williams, V.

AU - Walsh, Garry Michael

PY - 2009/12

Y1 - 2009/12

N2 - Background Eosinophil accumulation in the lung is an important feature of airway inflammation in asthma. There is therefore much interest in developing novel therapies to prevent this process. Accumulating evidence suggests that statins have anti-inflammatory properties, including inhibition of leucocyte accumulation. We therefore assessed the ability of five statins to inhibit human eosinophil adhesion to recombinant human inter-cellular adhesion molecule (rhICAM)-1 under physiologically relevant flow conditions. Methods Purified eosinophils were pre-treated with a panel of statins before elucidation of the adhesion profiles of resting and granulocyte macrophage-colony stimulating factor (GM-CSF)-stimulated cells to rhICAM-1-coated microchannels at a flow rate of 0.5 dynes/cm2. Images were recorded in real-time at 1 min intervals and analysed using Ducocell software. Results Fluvastatin and lovastatin (both 10 nm) significantly inhibited GM-CSF-stimulated eosinophil adhesion to rhICAM-1 after 2 min (34.4 +/- 3.0% inhibition and 37.8 +/- 12.6% inhibition, respectively, n=4, P < 0.05) but had no significant inhibitory effect on unstimulated eosinophil adhesion. Mevastatin, simvastatin, and pravastatin (all 10 nm) had no significant effect on GM-CSF-stimulated eosinophil adhesion to rhICAM-1. A concentration range of fluvastatin and lovastatin inhibited GM-CSF stimulated eosinophil adhesion with significant (P < 0.05) inhibition observed at low concentrations of 1 nm for both drugs. Mevalonate (100 nm) reversed fluvastatin-mediated but not lovastatin-mediated inhibition of eosinophil adhesion. Conclusions Inhibition of eosinophil adhesion to ICAM-1 by fluvastatin and lovastatin under physiological shear stress represent novel actions by these drugs that may inform the development of anti-inflammatory therapy for allergic disease. Cite this as: A. J. Robinson, D. Kashanin, F. O'Dowd, K. Fitzgerald, V. Williams and G. M. Walsh, Clinical & Experimental Allergy, 2009 (39) 1866-1874.

AB - Background Eosinophil accumulation in the lung is an important feature of airway inflammation in asthma. There is therefore much interest in developing novel therapies to prevent this process. Accumulating evidence suggests that statins have anti-inflammatory properties, including inhibition of leucocyte accumulation. We therefore assessed the ability of five statins to inhibit human eosinophil adhesion to recombinant human inter-cellular adhesion molecule (rhICAM)-1 under physiologically relevant flow conditions. Methods Purified eosinophils were pre-treated with a panel of statins before elucidation of the adhesion profiles of resting and granulocyte macrophage-colony stimulating factor (GM-CSF)-stimulated cells to rhICAM-1-coated microchannels at a flow rate of 0.5 dynes/cm2. Images were recorded in real-time at 1 min intervals and analysed using Ducocell software. Results Fluvastatin and lovastatin (both 10 nm) significantly inhibited GM-CSF-stimulated eosinophil adhesion to rhICAM-1 after 2 min (34.4 +/- 3.0% inhibition and 37.8 +/- 12.6% inhibition, respectively, n=4, P < 0.05) but had no significant inhibitory effect on unstimulated eosinophil adhesion. Mevastatin, simvastatin, and pravastatin (all 10 nm) had no significant effect on GM-CSF-stimulated eosinophil adhesion to rhICAM-1. A concentration range of fluvastatin and lovastatin inhibited GM-CSF stimulated eosinophil adhesion with significant (P < 0.05) inhibition observed at low concentrations of 1 nm for both drugs. Mevalonate (100 nm) reversed fluvastatin-mediated but not lovastatin-mediated inhibition of eosinophil adhesion. Conclusions Inhibition of eosinophil adhesion to ICAM-1 by fluvastatin and lovastatin under physiological shear stress represent novel actions by these drugs that may inform the development of anti-inflammatory therapy for allergic disease. Cite this as: A. J. Robinson, D. Kashanin, F. O'Dowd, K. Fitzgerald, V. Williams and G. M. Walsh, Clinical & Experimental Allergy, 2009 (39) 1866-1874.

KW - adhesion

KW - asthma

KW - eosinophils

KW - fluvastatin

KW - ICAM-1

KW - lovastatin

KW - statins

KW - antiinflammatory properties

KW - intercellular-adhesion

KW - epithelial-cells

KW - allergic-asthma

KW - expression

KW - simvastatin

KW - inflammation

KW - recruitment

KW - pathway

U2 - 10.1111/j.1365-2222.2009.03334.x

DO - 10.1111/j.1365-2222.2009.03334.x

M3 - Article

VL - 39

SP - 1866

EP - 1874

JO - Clinical & experimental allergy

JF - Clinical & experimental allergy

SN - 0954-7894

IS - 12

ER -