Xanthine oxidase increases neutrophil adherence to endothelial
cells by a dual icam-1 and p-selectin-mediated mechanism.
Terada, Lance S., Brooks M. Hybertson, Kevin G. Connelly, David Weill,
Dale Piermattei, John E. Repine.
Webb-Waring Institute for Biomedical Research and the Department of
Medicine at the University of Colorado Health Sciences Center,
Denver, CO.
APStracts 3:0554A, 1996.
Circulating xanthine oxidase (XO) can modify adhesive interactions
between neutrophils and the vascular endothelium, although the
mechanisms underlying this effect are not clear. We found that
treatment of bovine pulmonary artery endothelial cells (EC) but not
neutrophils or plasma with XO increased adherence, suggesting that XO
had its primary effect on EC. The mechanism by which XO increased
neutrophil adherence to EC involved binding of XO to EC and
production of H2O2. XO also increased PAF production by EC by a H2O2
-dependent mechanism. Likewise, the PAF receptor antagonist Web 2086
completely blocked XO-mediated neutrophil-EC adherence. In addition,
neutrophil adherence was dependent on the [beta]2 integrin Mac-1
(CD11b/CD18) but not LFA-1 (CD11a/CD18). Treatment of EC with XO for
30 min did not alter ICAM-1 surface expression but increased
expression of P-selectin and release of von Willibrand factor.
Antibodies against P-selectin (CD62) did not affect XO-mediated
neutrophil adherence under static conditions, but decreased both
rolling and firm adhesive interactions under conditions of shear. We
conclude that extracellular XO associates with the endothelium and
promotes neutrophil-endothelial cell interactions through dual ICAM-1
and P-selectin ligation, by a mechanism which involves PAF and H2O2
as intermediates.
Received 2 April 1996; accepted in final form 20 September 1996.
APS Manuscript Number A314-6.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996