Adenosine inhibits cytokine release and expression of adhesion
molecules by activated human endothelial cells.
Bouma, Maarten G., Frans A. J. M. Van Den Wildenberg, and Wim A.
Buurman.
Department of Surgery, University of Limburg, Maastricht, The
Netherlands
APStracts 2:0307C, 1995.
Ischemia induces excessive ATP catabolism with subsequent local
release of its metabolite adenosine, an autacoid with anti
-inflammatory properties. Since activation of the vascular endothelium
is critical to the inflammatory host response during ischemia and
reperfusion, the effects of adenosine on two major determinants of
endothelial cell activation, i.e. the release of proinflammatory
cytokines and the expression of adhesion molecules, were studied.
Adenosine dose-dependently inhibited the release of IL-6 and IL-8 by
stimulated human umbilical vein endothelial cells (HUVEC). Expression
of E-selectin and VCAM-1, but not ICAM-1, by activated HUVEC was also
reduced by adenosine. Inhibition of endogenous adenosine deaminase
activity by EHNA or 2'-deoxycoformycin strongly enhanced the
inhibitory effects of exogenous adenosine on cytokine release and
expression of E-selectin and VCAM-1. However, a clear role for
specific adenosine-receptors in the described inhibitory events could
not be established. Taken together, these data imply that the
vascular endothelium constitutes an important target for the anti
-inflammatory actions of adenosine.
Received 24 April 1995; accepted in final form 18 August 1995.
APS Manuscript Number C225-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 15 September 1995.