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SHR Neuro Krebs Kardio Lipid

Konya, V; Üllen, A; Kampitsch, N; Theiler, A; Philipose, S; Parzmair, GP; Marsche, G; Peskar, BA; Schuligoi, R; Sattler, W; Heinemann, A.
Endothelial E-type prostanoid 4 receptors promote barrier function and inhibit neutrophil trafficking.
J Allergy Clin Immunol. 2013; 131(2):532-40.e1-532-40.e2
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Autor/innen der Med Uni Graz:
Heinemann Akos
Kampitsch Nora
Konya Viktoria
Marsche Gunther
Parzmair Gerald Peter
Philipose Sonia
Sattler Wolfgang
Schuligoi Rufina
Theiler Anna
Üllen Andreas

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Background: Increased vascular permeability is a fundamental characteristic of inflammation. Substances that are released during inflammation, such as prostaglandin (PG) E-2, can counteract vascular leakage, thereby hampering tissue damage. Objective: In this study we investigated the role of PGE(2) and its receptors in the barrier function of human pulmonary microvascular endothelial cells and in neutrophil trafficking. Methods: Endothelial barrier function was determined based on electrical impedance measurements. Neutrophil recruitment was assessed based on adhesion and transendothelial migration. Morphologic alterations are shown by using immunofluorescence microscopy. Results: We observed that activation of E-type prostanoid (EP) 4 receptor by PGE(2) or an EP4-selective agonist (ONO AE1-329) enhanced the barrier function of human microvascular lung endothelial cells. EP4 receptor activation prompted similar responses in pulmonary artery and coronary artery endothelial cells. These effects were reversed by an EP4 antagonist (ONO AE3-208), as well as by blocking actin polymerization with cytochalasin B. The EP4 receptor-induced increase in barrier function was independent of the classical cyclic AMP/protein kinase A signaling machinery, endothelial nitric oxide synthase, and Rac1. Most importantly, EP4 receptor stimulation showed potent anti-inflammatory activities by (1) facilitating wound healing of pulmonary microvascular endothelial monolayers, (2) preventing junctional and cytoskeletal reorganization of activated endothelial cells, and (3) impairing neutrophil adhesion to endothelial cells and transendothelial migration. The latter effects could be partially attributed to reduced E-selectin expression after EP4 receptor stimulation. Conclusion: These data indicate that EP4 agonists as anti-inflammatory agents represent a potential therapy for diseases with increased vascular permeability and neutrophil extravasation. (J Allergy Clin Immunol 2013;131:532-40.)
Find related publications in this database (using NLM MeSH Indexing)
Actins - metabolism
Capillary Permeability - drug effects
Cell Adhesion - drug effects
Cell Movement - drug effects
Cells, Cultured -
Coronary Vessels - drug effects
Cyclic AMP - metabolism
Cyclic AMP-Dependent Protein Kinases - metabolism
Cytochalasin B - pharmacology
Dinoprostone - metabolism
Endothelial Cells - drug effects
Endothelium, Vascular - drug effects
Humans -
Lung - drug effects
Methyl Ethers - pharmacology
Microvessels - drug effects
Naphthalenes - pharmacology
Neutrophils - drug effects
Nitric Oxide Synthase Type III - metabolism
Phenylbutyrates - pharmacology
Pulmonary Artery - drug effects
Receptors, Prostaglandin E, EP4 Subtype - metabolism
Wound Healing - drug effects
rac1 GTP-Binding Protein - metabolism

Find related publications in this database (Keywords)
Chronic obstructive pulmonary disease
acute lung injury
endothelial barrier
vascular leakage
neutrophil trafficking
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