Superoxide mediates reperfusion-induced leukocyte-endothelial cell interactions.
The objective of this study was to determine whether superoxide mediates the leukocyte-endothelial cell interactions elicited by reperfusion (reoxygenation) of ischemic (hypoxic) tissues. Mesenteric and intestinal blood flows were reduced to 20% of control for 1 h, followed by 1 h of reperfusion. Sixty minutes after reperfusion, red blood cell velocity (Vr), leukocyte rolling velocity (Vw), and the number of adherent leukocytes were measured in mesenteric venules. Then, either human superoxide dismutase (hSOD), hydrogen peroxide-inactivated hSOD, or MoAb IB4 (a monoclonal antibody against the leukocyte adhesion molecule CD18) was injected intravenously. Ten minutes later, repeat measurements were obtained and compared with pretreatment values. hSOD attenuated reperfusion-induced neutrophil adherence and increased Vw/Vr, an index of the fracture stress between leukocytes and endothelium. Peroxide-inactivated hSOD did not alter any parameter. MoAb IB4 attenuated reperfusion-induced adherence but did not alter Vw/Vr. In a correlate study, cultured bovine microvascular endothelium was exposed to 30 min of anoxia, followed by 60 min of reoxygenation. Cat neutrophils were added during reoxygenation. Reoxygenation-induced leukocyte adherence was attenuated by either hSOD or MoAb IB4 but not by inactivated hSOD. Adherence of phorbol 12-myristate 13-acetate-activated cat neutrophils to plastic was unaffected by hSOD or inactive hSOD, yet MoAb IB4 virtually abolished the response. These results indicate that superoxide mediates reperfusion-induced leukocyte adherence and that endothelial cells are required for this superoxide-mediated adherence.
Suzuki
M
M
Department of Physiology, Louisiana State University Medical Center, Shreveport 71130.
Inauen
W
W
Kvietys
P R
PR
Grisham
M B
MB
Meininger
C
C
Schelling
M E
ME
Granger
H J
HJ
Granger
D N
DN
D000818:Animals; D002415:Cats; D002448:Cell Adhesion; D002450:Cell Communication / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology; D007962:Leukocytes / Q000502:physiology*; D015424:Reperfusion; D013152:Splanchnic Circulation; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*
D013481:Superoxides; D013482:Superoxide Dismutase