The role of prostacyclin in the interaction of endothelial cells and eosinophil granulocytes
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BioMed Central Page 1 of 1 (page number not for citation purposes) BMC Pharmacology Open Access Meeting abstract The role of prostacyclin in the interaction of endothelial cells and eosinophil granulocytes Viktória Kónya 1 , Eva M Sturm 1 , Zoltán Bálint 2 , Martin Krenn 3 and Ákos Heinemann* 1 Address: 1 Institute of Experimental and Clinical Pharmacology, Medical University of Graz, 8010 Graz, Austria, 2 Department of Anaesthesiology, Medical University of Graz, 8036 Graz, Austria and 3 Institute of Pharmacology and Toxicology, University of Graz, 8010 Graz, Austria Email: Ákos Heinemann* - [email protected] * Corresponding author Background Enhanced eosinophil migration from the blood into the tissue is a hallmark of bronchial asthma and other allergic diseases. So far, very little is known how the function of vascular endothelial cells is modulated in this process. Our aim was to characterize the role of prostacyclin (PGI 2 ) in endothelial function and endothelium-eosi- nophil interaction. Materials and methods Cell interaction studies, like adhesion and transmigration assays, were performed with freshly isolated human blood eosinophils on confluent layers of human lung microvas- cular endothelial cells. The changes in endothelial monol- ayer integrity were detected by means of transendothelial electrical resistance and by fluorescence microscopy. Results Under basal conditions, the major prostaglandin released by human microvascular endothelial cells is PGI 2 . Exoge- nous PGI 2 markedly attenuated the migration of isolated eosinophils through cell-free filters. This effect was pre- vented by the IP receptor antagonist Cay10441 and the adenylyl cyclase inhibitor SQ29548. Treatment of endothelial cells with diclofenac, a non-selective COX inhibitor, abolished the PGI 2 production which was accompanied by enhanced eosinophil adhesion to endothelial monolayers. Similarly, the transmigration of eosinophils through endothelial monolayers was enhanced by diclofenac. The diclofenac treatment itself decreased the electrical resistance of endothelial monolay- ers and compromised the intercellular cell junctions as visualized by VE-cadherin staining. Conclusion Based on these observations, we conclude that the basal synthesis of PGI 2 by endothelial cells can down-regulate the endothelial adhesion and transmigration of eosi- nophils. Furthermore, endogenous PGI 2 seems to be important for the maintenance of endothelium barrier function. These results suggest that PGI 2 may have a pro- tective role in the case of allergic inflammation and pro- vide a novel explanation for previous observations that IP knock-out mice show enhanced eosinophilic inflamma- tion in response to allergen [1]. References 1. Takahashi Y, Tokuoka S, Masuda T, Hirano Y, Nagao M, Tanaka H, Inagaki N, Narumiya S, Nagai H: Augmentation of allergic inflam- mation in prostanoid IP receptor deficient mice. Br J Pharma- col 2002, 137:315-322. from 14 th Scientific Symposium of the Austrian Pharmacological Society (APHAR) Innsbruck, Austria. 21–22 November 2008 Published: 5 November 2008 BMC Pharmacology 2008, 8(Suppl 1):A13 doi:10.1186/1471-2210-8-S1-A13 <supplement> <title> <p>14<sup>th </sup>Scientific Symposium of the Austrian Pharmacological Society (APHAR)</p> </title> <editor>Andrea Laslop and Thomas Griesbacher</editor> <note>Meeting abstracts – A single PDF containing all abstracts in this Supplement is available <a href="http://www.biomedcentral.com/content/files/pdf/1471-2210-8-S1-full.pdf">here</a>.</note> <url>http://www.biomedcentral.com/content/pdf/1471-2210-8-S1-info.pdf</url> </supplement> This abstract is available from: http://www.biomedcentral.com/1471-2210/8/S1/A13 © 2008 Kónya et al; licensee BioMed Central Ltd.
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Transcript of The role of prostacyclin in the interaction of endothelial cells and eosinophil granulocytes
BioMed Central
Page 1 of 1(page number not for citation purposes)
BMC Pharmacology
Open AccessMeeting abstractThe role of prostacyclin in the interaction of endothelial cells and eosinophil granulocytesViktória Kónya1, Eva M Sturm1, Zoltán Bálint2, Martin Krenn3 and Ákos Heinemann*1
Address: 1Institute of Experimental and Clinical Pharmacology, Medical University of Graz, 8010 Graz, Austria, 2Department of Anaesthesiology, Medical University of Graz, 8036 Graz, Austria and 3Institute of Pharmacology and Toxicology, University of Graz, 8010 Graz, Austria
Email: Ákos Heinemann* - [email protected]
* Corresponding author
BackgroundEnhanced eosinophil migration from the blood into thetissue is a hallmark of bronchial asthma and other allergicdiseases. So far, very little is known how the function ofvascular endothelial cells is modulated in this process.Our aim was to characterize the role of prostacyclin(PGI2) in endothelial function and endothelium-eosi-nophil interaction.
Materials and methodsCell interaction studies, like adhesion and transmigrationassays, were performed with freshly isolated human bloodeosinophils on confluent layers of human lung microvas-cular endothelial cells. The changes in endothelial monol-ayer integrity were detected by means of transendothelialelectrical resistance and by fluorescence microscopy.
ResultsUnder basal conditions, the major prostaglandin releasedby human microvascular endothelial cells is PGI2. Exoge-nous PGI2 markedly attenuated the migration of isolatedeosinophils through cell-free filters. This effect was pre-vented by the IP receptor antagonist Cay10441 and theadenylyl cyclase inhibitor SQ29548. Treatment ofendothelial cells with diclofenac, a non-selective COXinhibitor, abolished the PGI2 production which wasaccompanied by enhanced eosinophil adhesion toendothelial monolayers. Similarly, the transmigration of
eosinophils through endothelial monolayers wasenhanced by diclofenac. The diclofenac treatment itselfdecreased the electrical resistance of endothelial monolay-ers and compromised the intercellular cell junctions asvisualized by VE-cadherin staining.
ConclusionBased on these observations, we conclude that the basalsynthesis of PGI2 by endothelial cells can down-regulatethe endothelial adhesion and transmigration of eosi-nophils. Furthermore, endogenous PGI2 seems to beimportant for the maintenance of endothelium barrierfunction. These results suggest that PGI2 may have a pro-tective role in the case of allergic inflammation and pro-vide a novel explanation for previous observations that IPknock-out mice show enhanced eosinophilic inflamma-tion in response to allergen [1].
References1. Takahashi Y, Tokuoka S, Masuda T, Hirano Y, Nagao M, Tanaka H,
Inagaki N, Narumiya S, Nagai H: Augmentation of allergic inflam-mation in prostanoid IP receptor deficient mice. Br J Pharma-col 2002, 137:315-322.
from 14th Scientific Symposium of the Austrian Pharmacological Society (APHAR)Innsbruck, Austria. 21–22 November 2008
Published: 5 November 2008
BMC Pharmacology 2008, 8(Suppl 1):A13 doi:10.1186/1471-2210-8-S1-A13
<supplement> <title> <p>14<sup>th </sup>Scientific Symposium of the Austrian Pharmacological Society (APHAR)</p> </title> <editor>Andrea Laslop and Thomas Griesbacher</editor> <note>Meeting abstracts – A single PDF containing all abstracts in this Supplement is available <a href="http://www.biomedcentral.com/content/files/pdf/1471-2210-8-S1-full.pdf">here</a>.</note> <url>http://www.biomedcentral.com/content/pdf/1471-2210-8-S1-info.pdf</url> </supplement>
This abstract is available from: http://www.biomedcentral.com/1471-2210/8/S1/A13
© 2008 Kónya et al; licensee BioMed Central Ltd.
