Sialyl Lewis(x) oligosaccharide reduces ischemia-reperfusion injury in the rabbit ear.
Ischemia-reperfusion injury in the rabbit ear is neutrophil (PMN)-mediated, and is significantly reduced by anti-adhesion agents directed against beta 2 integrins, P-selectin, or L-selectin. We further examined selectin-mediated adherence in this setting following the administration of soluble sialyl Lewis(x) (SLe(x)), the principal carbohydrate ligand for P-, L-, and E-selectin, at various times following reperfusion. Under constant ambient temperature conditions, the rabbit ear vascular supply was isolated and occluded with an atraumatic vascular clamp for 6 h, then allowed to reperfuse. Animals receiving i.v. SLe(x) (25 mg/kg bolus + 50 mg/kg infusion over 10 h) 1) at the time of reperfusion, 2) 1 h after reperfusion, 3) 4 h after reperfusion, or 4) 12 h after reperfusion were compared with control animals receiving either saline or sialyl lactosamine, an oligosaccharide structurally similar to SLe(x) but not involved in selectin recognition. Tissue injury was assessed by serial measurement of ear edema and by visual determination of ear necrosis over 7 days. Tissue edema and necrosis were significantly reduced in animals treated with SLe(x) immediately upon reperfusion or after a 1-h delay, but not in animals for whom SLe(x) administration was delayed by 4 or 12 h. Furthermore, SLe(x) administration alone had no effect on circulating leukocyte or PMN counts, or PMN expression of CD18 or L-selectin. We conclude that interruption of selectin-mediated adherence with soluble SLe(x) oligosaccharide attenuates reperfusion in the rabbit ear. The observation that SLe(x) is efficacious only if administered in the first hour after reperfusion suggests that the more immediately available P- and L-selectin participate in this PMN adhesion/injury process, whereas E-selectin, with its delayed endothelial expression, does not.
Han
K T
KT
Department of Plastic and Reconstructive Surgery, Catholic University Medical College, Seoul, Korea.
Sharar
S R
SR
Phillips
M L
ML
Harlan
J M
JM
Winn
R K
RK
D000606:Amino Sugars / Q000627:therapeutic use; D000818:Animals; D018821:CD18 Antigens / Q000187:drug effects; D004423:Ear / Q000098:blood supply*; D019041:L-Selectin / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects; D007983:Lewis Blood Group Antigens / Q000276:immunology*; D016256:Lewis X Antigen / Q000097:blood / Q000276:immunology*; D009844:Oligosaccharides / Q000097:blood / Q000276:immunology / Q000627:therapeutic use*; D011817:Rabbits; D015427:Reperfusion Injury / Q000517:prevention & control*; D000080506:Sialyl Lewis X Antigen
D000606:Amino Sugars; D018821:CD18 Antigens; D007983:Lewis Blood Group Antigens; D016256:Lewis X Antigen; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen; D019041:L-Selectin; C032233:lactosamine