Endogenous nitric oxide decreases xanthine oxidase- mediated
neutrophil adherence: role of p-selectin.
Terada, Lance S., John E. Repine, Dale Piermattei, Brooks M.
Hybertson.
Webb-Waring Institute for Biomedical Research, University of
Colorado Health Sciences Center, Box C322, 4200 E. Ninth Ave.,
Denver, CO 80262
APStracts 3:0499A, 1996.
The oxygen radical producing enzyme xanthine oxidase (XO) can promote
neutrophil adherence to endothelium. Recognizing that a balance often
exists in inflammatory processes, we sought to determine whether XO
initiates anti-adherent pathways. We found that bovine pulmonary
artery endothelial cells (EC) exposed to XO released increased
amounts of nitrite into the media, reflecting an increased production
of nitric oxide (NO). When EC were subjected to shear stress,
treatment with XO and/or the NO synthase inhibitor N -nitro-L
-arginine (NLA) increased neutrophil rolling behavior and firm
neutrophil adherence to EC in an additive fashion. Both rolling and
adherent interactions were abolished by monoclonal antibodies
directed against P-selectin. In addition, treatment of EC with XO
and/or NLA increased both surface expression of P-selectin and
release of von Willebrand factor (vWF) into media. Finally, treatment
of EC with the NO donor sodium nitroprusside decreased XO-mediated
neutrophil rolling and adherence. We conclude that XO stimulates EC
to produce NO, and that NO decreases the P-selectin dependent
neutrophil adhesion initiated by XO. Such increases in endogenous NO
may constitute an important negative feedback response to the acute
proadhesive effects of XO.
Received 30 July 1996; accepted in final form 25 October 1996
APS Manuscript Number A732-6.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 November 1996