Exogenous NO enhances hydrogen peroxide-mediated neutrophil adherence to cultured endothelial cells.
One important aspect of oxidant injury is the enhancement of neutrophil-endothelial adhesion by oxidants such as hydrogen peroxide. Recent studies suggest that nitric oxide (NO) can limit oxidant-mediated tissue injury, since inhibitors of endogenous NO synthesis often promote neutrophil-endothelial adhesion. However, less is known about the direct role of exogenous NO in modulating proadhesive effects of oxidants. The objective of this study was to examine how an NO donor modifies hydrogen peroxide-mediated adhesion of neutrophils to cultured endothelial cells. Human umbilical vein endothelial cell monolayers were exposed for 30 min to 0-0.1 mM hydrogen peroxide with or without the NO donor spermine-NONOate (SNO; 0-0.5 mM), and the adhesion of 51Cr-labeled polymorphonuclear neutrophils (PMNs) was measured in a static adhesion assay. PMN adherence was not altered by either peroxide (up to 0.1 mM) or SNO (up to 0.5 mM) alone but was significantly increased by over 300% by coadministration of both 0.1 mM peroxide and 0.5 mM SNO. This increase in adhesion with these two agents was correlated with an increase in the presentation of surface P-selectin but not intercellular adhesion molecule-1. Both PMN adhesion and P-selectin presentation were blocked by 0.1 mM desferrioxamine (an iron chelator) and 1 mM methionine (an oxyradical scavenger). WEB-2086, a platelet-activating factor-receptor antagonist (10 microM), also prevented PMN adhesion but not P-selectin expression. An antibody directed against either P-selectin or intercellular adhesion molecule-1 also blocked adhesion. These data indicate that NO may actually exacerbate rather than protect against the inflammatory effects of peroxide in some models of inflammation through the synthesis of platelet-activating factor and the mobilization of P-selectin.
Okayama
N
N
Department of Molecular and Cellular Physiology, Louisiana State University Medical Center, Shreveport 71130-3932, USA.
Ichikawa
H
H
Coe
L
L
Itoh
M
M
Alexander
J S
JS
D001381:Azepines / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D003676:Deferoxamine / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008715:Methionine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology*; D009569:Nitric Oxide / Q000494:pharmacology*; D009589:Nitrogen Oxides; D019007:P-Selectin / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D013096:Spermine / Q000031:analogs & derivatives / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D015815:Cell Adhesion Molecules; D009589:Nitrogen Oxides; D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D014230:Triazoles; C052518:WEB 2086; C091861:spermine nitric oxide complex; D013096:Spermine; D009569:Nitric Oxide; D008715:Methionine; D006861:Hydrogen Peroxide; D003676:Deferoxamine