Endothelium-derived prostaglandin I(2) controls the migration of eosinophils.
BACKGROUND
Enhanced eosinophil migration from the blood into the tissue is a hallmark of allergic diseases. Prostaglandin (PG) I(2) is the major prostanoid released by endothelial cells. Mice deficient in PGI(2) receptors (IPs) show exaggerated eosinophilic inflammation in response to allergen.


OBJECTIVE
We set out to determine the role of PGI(2) in eosinophil trafficking.


METHODS
Human lung microvascular endothelial cells and purified human eosinophils were used to study adhesion and transendothelial migration. Morphologic studies were performed with fluorescence microscopy.


RESULTS
PGI(2) markedly attenuated the migration of eosinophils through cell-free filters but had no effect on neutrophil migration. The inhibitory effect of PGI(2) on eosinophils was prevented by the IP antagonist Cay10441 and the adenylyl cyclase inhibitor SQ22536. Similarly, PGI(2) prevented the adhesion of eosinophils to fibronectin and the rapid upregulation and activation of the adhesion molecule CD11b. IP expression on eosinophils was confirmed by means of flow cytometry and Western blotting. Furthermore, when endothelial cells were treated with the COX inhibitor diclofenac to abolish PGI(2) production, adhesion of eosinophils to endothelial monolayers and subsequent transendothelial migration were markedly enhanced. Similarly, the IP antagonist enhanced eosinophil adhesion to endothelial cells. Inhibition of PGI(2) biosynthesis decreased the electrical resistance of endothelial monolayers and compromised the texture of adherent junctions, as visualized by means of VE-cadherin and F-actin staining.


CONCLUSIONS
We propose that endothelium-derived PGI(2) might be fundamental for the maintenance of the endothelial barrier function against infiltrating cells. These results suggest that selective IP agonists might have beneficial effects in allergic inflammation.
Institute of Experimental and Clinical Pharmacology, Medical University Graz, A-8010 Graz, Austria.
Viktoria
V
Konya
Eva M
EM
Sturm
Petra
P
Schratl
Eckhard
E
Beubler
Gunther
G
Marsche
Rufina
R
Schuligoi
Irmgard Th
IT
Lippe
Bernhard A
BA
Peskar
Akos
A
Heinemann
D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D004804:Eosinophils / Q000187:drug effects / Q000502:physiology*; D011464:Epoprostenol / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008168:Lung / Q000098:blood supply / Q000166:cytology / Q000276:immunology
D011464:Epoprostenol