Journal
SHOCK
Volume 15, Issue 4, Pages 297-301Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/00024382-200115040-00008
Keywords
NECA; beta(2) integrins; ICAM-1; endothelial cells; FITC-Dextran
Ask authors/readers for more resources
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 A(2B) receptors. The inhibitory effect of adenosine was reversed by 3,7-dimethyl-1-propargylxanthine, an A(2) receptor antagonist. Adenosine (100 muM) or the A(2B) receptor agonist 5'-N-ethylcarboxamidoadenosine (NECA, 100 muM) significantly reduced PMN transendothelial migration. However. expression of activated PMN beta (2) integrins and HUVEC ICAM-1 were not significantly altered by adenosine or NECA. Adenosine attenuates human PMN VEGF release and transendothelial migration via the A(2B) receptor. This provides a novel target for the modulation of PMN-directed vascular hyperpermeability in conditions such as the capillary leak syndrome.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available