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Open Access

Inhibitory effects of prostaglandin EP4 receptors on human eosinophils

  • Petra Luschnig-Schratl1,
  • Eva M Sturm1,
  • Viktória Kónya1,
  • Rufina Schuligoi1 and
  • Ákos Heinemann1Email author
BMC Pharmacology20099(Suppl 2):A2

https://doi.org/10.1186/1471-2210-9-S2-A2

Published: 12 November 2009

Background

The accumulation of eosinophils in lung tissue is a hallmark of asthma, and it is believed that eosinophils play a crucial pathogenic role in allergic inflammation. Prostaglandin (PG) E2 exerts anti-inflammatory and broncho-protective mechanisms in asthma, but the underlying mechanisms have remained unclear. We have shown previously that PGE2 and the EP2 receptor agonist butaprost inhibit eosinophil trafficking in vitro and in vivo.

Methods

Human eosinophils were purified by negative magnetic selection from peripheral blood. Cell migration was determined in microBoyden chemotaxis chambers. Ca2+ flux and expression of cell surface markers was recorded by flow cytometry. EP4 receptor expression was demonstrated by immunostaining.

Results

The chemotaxis of eosinophils towards eotaxin and C5a was attenuated by the EP4 agonist ONO-AE1-329, and the EP4 antagonists ONO-AE3-208 and GW627368x partially reversed the inhibitory effect of PGE2 on eosinophil migration. ONO-AE1-329, and also PGE2, but not butaprost, inhibited the Ca2+ flux and the production of reactive oxygen species in eosinophils. ONO-AE1-329 also inhibited eosinophil degranulation and the up-regulation of the adhesion molecule CD11b. Selective kinase inhibitors revealed that the inhibitory effect of EP4 stimulation on eosinophil migration depended upon activation of phosphatidylinositol 3-kinase and protein kinase C, but not cAMP. Immunostaining showed that human eosinophils express EP4 receptors and that EP4 receptor expression in the murine lungs is prominent in airway epithelium, and after allergen challenge, in peribronchial infiltrating leukocytes.

Conclusion

These data show that EP4 receptor agonists potently inhibit eosinophil trafficking and activation, and might hence be a useful therapeutic option in eosinophilic diseases.

Authors’ Affiliations

(1)
Institute of Experimental and Clinical Pharmacology, Medical University of Graz

Copyright

© Luschnig-Schratl et al; licensee BioMed Central Ltd. 2009

This article is published under license to BioMed Central Ltd.

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