Role of superoxide in hemorrhagic shock-induced P-selectin expression

Superoxide has been implicated in the regulation of endothelial cell adhesi on molecule expression and the subsequent initiation of leukocyte-endotheli al cell adhesion in different experimental models of inflammation. The obje ctive of this study was to assess the contribution of oxygen radicals to P- selectin expression in a murine model of whole body ischemia-reperfusion, i .e., hemorrhage-resuscitation (H/R), with the use of different strategies t hat interfere with either the production (allopurinol, CD11/CD18-deficient or p47(phox)-/- mice) or accumulation [intravenous superoxide dismutase (SO D), mutant mice that overexpress SOD] of oxygen radicals. P-selectin expres sion was quantified in different regional vascular beds by use of the dual- radiolabeled monoclonal antibody technique. H/R elicited a significant incr ease in P-selectin expression in all vascular beds. This response was blunt ed in SOD transgenic mice and in wild-type mice receiving either intravenou s SOD or the xanthine oxidase inhibitor allopurinol. Mice genetically defic ient in either a subunit of NADPH oxidase or the leukocyte adhesion molecul e CD11/CD18 also exhibited a reduced P-selectin expression. These results i mplicate superoxide, derived from both xanthine oxidase and NADPH oxidase, as mediators of the increased P-selectin expression observed in different r egional vascular beds exposed to hemorrhage and retransfusion.