Role of superoxide in hemorrhagic shock-induced P-selectin expression.
Superoxide has been implicated in the regulation of endothelial cell adhesion molecule expression and the subsequent initiation of leukocyte-endothelial cell adhesion in different experimental models of inflammation. The objective 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 that interfere with either the production (allopurinol, CD11/CD18-deficient or p47(phox)-/- mice) or accumulation [intravenous superoxide dismutase (SOD), mutant mice that overexpress SOD] of oxygen radicals. P-selectin expression was quantified in different regional vascular beds by use of the dual-radiolabeled monoclonal antibody technique. H/R elicited a significant increase in P-selectin expression in all vascular beds. This response was blunted in SOD transgenic mice and in wild-type mice receiving either intravenous SOD or the xanthine oxidase inhibitor allopurinol. Mice genetically deficient in either a subunit of NADPH oxidase or the leukocyte adhesion molecule CD11/CD18 also exhibited a reduced P-selectin expression. These results implicate superoxide, derived from both xanthine oxidase and NADPH oxidase, as mediators of the increased P-selectin expression observed in different regional vascular beds exposed to hemorrhage and retransfusion.
Department of Pediatric Surgery, School of Medicine, Dokuz Eylül University, Izmir, Turkey 35340, USA.
F M
FM
Akgür
M F
MF
Brown
G B
GB
Zibari
J C
JC
McDonald
C J
CJ
Epstein
C R
CR
Ross
D N
DN
Granger
D000818:Animals; D000911:Antibodies, Monoclonal; D018845:CD11 Antigens / Q000235:genetics / Q000502:physiology; D018821:CD18 Antigens / Q000235:genetics / Q000502:physiology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009245:NADH Dehydrogenase / Q000378:metabolism; D019255:NADPH Oxidases; D019007:P-Selectin / Q000096:biosynthesis*; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012771:Shock, Hemorrhagic / Q000503:physiopathology*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D018845:CD11 Antigens; D018821:CD18 Antigens; D019007:P-Selectin; D010750:Phosphoproteins; D013481:Superoxides; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D009245:NADH Dehydrogenase