Adenosine inhibits neutrophil vascular endothelial growth factor release and transendothelial migration via A2B receptor activation.

Hdl Handle:
http://hdl.handle.net/10147/209084
Title:
Adenosine inhibits neutrophil vascular endothelial growth factor release and transendothelial migration via A2B receptor activation.
Authors:
Wakai, A; Wang, J H; Winter, D C; Street, J T; O'Sullivan, R G; Redmond, H P
Affiliation:
Department of Academic Surgery, Cork University Hospital, Cork, Republic of, Ireland.
Citation:
Shock. 2001 Apr;15(4):297-301.
Journal:
Shock (Augusta, Ga.)
Issue Date:
3-Feb-2012
URI:
http://hdl.handle.net/10147/209084
PubMed ID:
11303729
Abstract:
The effects of adenosine on neutrophil (polymorphonuclear neutrophils; PMN)-directed changes in vascular permeability are poorly characterized. This study investigated whether adenosine modulates activated PMN vascular endothelial growth factor (vascular permeability factor; VEGF) release and transendothelial migration. PMN activated with tumour necrosis factor-alpha (TNF-alpha, 10 ng/mL) were incubated with adenosine and its receptor-specific analogues. Culture supernatants were assayed for VEGF. PMN transendothelial migration across human umbilical vein endothelial cell (HUVEC) monolayers was assessed in vitro. Adhesion molecule receptor expression was assessed flow cytometrically. Adenosine and some of its receptor-specific analogues dose-dependently inhibited activated PMN VEGF release. The rank order of potency was consistent with the affinity profile of human A2B receptors. The inhibitory effect of adenosine was reversed by 3,7-dimethyl-1-propargylxanthine, an A2 receptor antagonist. Adenosine (100 microM) or the A2B receptor agonist 5'-N-ethylcarboxamidoadenosine (NECA, 100 microM) significantly reduced PMN transendothelial migration. However, expression of activated PMN beta2 integrins and HUVEC ICAM-1 were not significantly altered by adenosine or NECA. Adenosine attenuates human PMN VEGF release and transendothelial migration via the A2B receptor. This provides a novel target for the modulation of PMN-directed vascular hyperpermeability in conditions such as the capillary leak syndrome.
Language:
eng
MeSH:
Adenosine/*analogs & derivatives/*pharmacology; Adenosine-5'-(N-ethylcarboxamide)/pharmacology; Antigens, CD18/physiology; Cell Movement/drug effects; Cells, Cultured/drug effects; Chemotaxis, Leukocyte/*drug effects; Depression, Chemical; Dose-Response Relationship, Drug; Endothelial Growth Factors/*secretion; Endothelium, Vascular/cytology; Humans; Intercellular Adhesion Molecule-1/biosynthesis; Lymphokines/*secretion; N-Formylmethionine Leucyl-Phenylalanine/pharmacology; Neutrophils/cytology/*drug effects/secretion; Phenethylamines/pharmacology; Purinergic P1 Receptor Agonists; Purinergic P1 Receptor Antagonists; Receptor, Adenosine A2B; Receptors, Purinergic P1/*drug effects/physiology; Recombinant Proteins/pharmacology; Theobromine/analogs & derivatives/pharmacology; Tumor Necrosis Factor-alpha/genetics/pharmacology; Umbilical Veins; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors
ISSN:
1073-2322 (Print); 1073-2322 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorWakai, Aen_GB
dc.contributor.authorWang, J Hen_GB
dc.contributor.authorWinter, D Cen_GB
dc.contributor.authorStreet, J Ten_GB
dc.contributor.authorO'Sullivan, R Gen_GB
dc.contributor.authorRedmond, H Pen_GB
dc.date.accessioned2012-02-03T15:11:50Z-
dc.date.available2012-02-03T15:11:50Z-
dc.date.issued2012-02-03T15:11:50Z-
dc.identifier.citationShock. 2001 Apr;15(4):297-301.en_GB
dc.identifier.issn1073-2322 (Print)en_GB
dc.identifier.issn1073-2322 (Linking)en_GB
dc.identifier.pmid11303729en_GB
dc.identifier.urihttp://hdl.handle.net/10147/209084-
dc.description.abstractThe effects of adenosine on neutrophil (polymorphonuclear neutrophils; PMN)-directed changes in vascular permeability are poorly characterized. This study investigated whether adenosine modulates activated PMN vascular endothelial growth factor (vascular permeability factor; VEGF) release and transendothelial migration. PMN activated with tumour necrosis factor-alpha (TNF-alpha, 10 ng/mL) were incubated with adenosine and its receptor-specific analogues. Culture supernatants were assayed for VEGF. PMN transendothelial migration across human umbilical vein endothelial cell (HUVEC) monolayers was assessed in vitro. Adhesion molecule receptor expression was assessed flow cytometrically. Adenosine and some of its receptor-specific analogues dose-dependently inhibited activated PMN VEGF release. The rank order of potency was consistent with the affinity profile of human A2B receptors. The inhibitory effect of adenosine was reversed by 3,7-dimethyl-1-propargylxanthine, an A2 receptor antagonist. Adenosine (100 microM) or the A2B receptor agonist 5'-N-ethylcarboxamidoadenosine (NECA, 100 microM) significantly reduced PMN transendothelial migration. However, expression of activated PMN beta2 integrins and HUVEC ICAM-1 were not significantly altered by adenosine or NECA. Adenosine attenuates human PMN VEGF release and transendothelial migration via the A2B receptor. This provides a novel target for the modulation of PMN-directed vascular hyperpermeability in conditions such as the capillary leak syndrome.en_GB
dc.language.isoengen_GB
dc.subject.meshAdenosine/*analogs & derivatives/*pharmacologyen_GB
dc.subject.meshAdenosine-5'-(N-ethylcarboxamide)/pharmacologyen_GB
dc.subject.meshAntigens, CD18/physiologyen_GB
dc.subject.meshCell Movement/drug effectsen_GB
dc.subject.meshCells, Cultured/drug effectsen_GB
dc.subject.meshChemotaxis, Leukocyte/*drug effectsen_GB
dc.subject.meshDepression, Chemicalen_GB
dc.subject.meshDose-Response Relationship, Drugen_GB
dc.subject.meshEndothelial Growth Factors/*secretionen_GB
dc.subject.meshEndothelium, Vascular/cytologyen_GB
dc.subject.meshHumansen_GB
dc.subject.meshIntercellular Adhesion Molecule-1/biosynthesisen_GB
dc.subject.meshLymphokines/*secretionen_GB
dc.subject.meshN-Formylmethionine Leucyl-Phenylalanine/pharmacologyen_GB
dc.subject.meshNeutrophils/cytology/*drug effects/secretionen_GB
dc.subject.meshPhenethylamines/pharmacologyen_GB
dc.subject.meshPurinergic P1 Receptor Agonistsen_GB
dc.subject.meshPurinergic P1 Receptor Antagonistsen_GB
dc.subject.meshReceptor, Adenosine A2Ben_GB
dc.subject.meshReceptors, Purinergic P1/*drug effects/physiologyen_GB
dc.subject.meshRecombinant Proteins/pharmacologyen_GB
dc.subject.meshTheobromine/analogs & derivatives/pharmacologyen_GB
dc.subject.meshTumor Necrosis Factor-alpha/genetics/pharmacologyen_GB
dc.subject.meshUmbilical Veinsen_GB
dc.subject.meshVascular Endothelial Growth Factor Aen_GB
dc.subject.meshVascular Endothelial Growth Factorsen_GB
dc.titleAdenosine inhibits neutrophil vascular endothelial growth factor release and transendothelial migration via A2B receptor activation.en_GB
dc.contributor.departmentDepartment of Academic Surgery, Cork University Hospital, Cork, Republic of, Ireland.en_GB
dc.identifier.journalShock (Augusta, Ga.)en_GB
dc.description.provinceMunster-

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