Molecular mechanisms involved in superoxide-induced leukocyte-endothelial cell interactions in vivo.
Intravital microscopy was used to monitor leukocyte adherence, flux, rolling velocity, and number of rolling leukocytes (flux/velocity) in venules 25-40 microns in diameter. The superoxide-generating system, hypoxanthine and xanthine oxidase (HX/XO), was infused into the mesenteric circulation in untreated animals or in animals pretreated with either catalase (a hydrogen peroxide scavenger), WEB-2086 [a platelet-activating factor (PAF) receptor antagonist], or monoclonal antibodies directed against adhesion molecules CD18 (CL26) or P-selectin (PB1.3). HX/XO infusion caused a decrease in leukocyte rolling velocity and an increase in the number of rolling and adherent leukocytes. WEB-2086 prevented the increase in leukocyte adhesion and markedly increased leukocyte rolling velocity. PB1.3 abolished the HX/XO-associated rise in the flux of rolling leukocytes and proportionally decreased the number of adherent leukocytes. CL26 abolished HX/XO-induced leukocyte adhesion and also reduced the number of rolling leukocytes. In conclusion, P-selectin mediates the increased leukocyte flux induced by superoxide, whereas PAF and CD18 modulate leukocyte adhesion. PAF also reduces leukocyte rolling velocity, possibly as a result of CD18, but not P-selectin.
Gaboury
J P
JP
Department of Medical Physiology, University of Calgary, Alberta, Canada.
Anderson
D C
DC
Kubes
P
P
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D018821:CD18 Antigens; D002374:Catalase / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D016166:Free Radical Scavengers; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D016028:Receptors, Leukocyte-Adhesion / Q000502:physiology; D013152:Splanchnic Circulation; D013481:Superoxides / Q000378:metabolism / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D001381:Azepines; D018821:CD18 Antigens; D016166:Free Radical Scavengers; D007042:Hypoxanthines; D010972:Platelet Activating Factor; D016028:Receptors, Leukocyte-Adhesion; D014230:Triazoles; C052518:WEB 2086; D013481:Superoxides; D019271:Hypoxanthine; D002374:Catalase; D014969:Xanthine Oxidase