EFFECT OF OLIGOSACCHARIDES ON REJECTION AND REPERFUSION INJURY AFTER LUNG TRANSPLANTATION

Background. During rejection and reperfusion injury, infiltration of l eukocytes into the lung allograft is regulated by adhesion molecules, especially selectins. Sialyl-Lewis X (SLX), an oligosaccharide, is a m embrane ligand molecule of P-selectin adhesion receptors. In this stud y, we investigated the effect of intravenous administration of a synth etic oligosaccharide analog of SLX on rejection and reperfusion injury after rat lung transplantation. Methods. Left lateral, orthotopic, al logeneic lung transplantation was performed between fully incompatible rat strains (Dark Agouti --> Lewis) after an average total ischemic t ime of 45 minutes. Group A (n = 6) served as control; no immunosuppres sion was used. In group B (n = 6), rats received 200 mu g/kg/day SLX i ntravenously on days 0 to 4. The animals were killed on days 5 and 10, respectively. In groups C and D, syngeneic lung transplantation was p erformed (Lewis --> Lewis), with an ischemic time of 7 hours. Group C (n = 6) served as untreated controls. Group D rats (n = 6) received a single dose of 20 mg/kg SLX at the end of the ischemic time. The anima ls were killed on days 2 and 5, respectively. Results. In group B rats , treated for rejection, a lower grade of rejection (2.7 +/- 0.6 vs 4. 0 +/- 0.0, p < 0.05) and fewer infiltrating CD11a-positive leukocytes (6.6 +/- 2.7 vs 18.6 +/- 7.3, p < 0.05) were found histologically comp ared with group A. In group D rats, treated for reperfusion injury, a significant reduction of reperfusion injury was detected on chest radi ograms and by histologic study. Conclusions. A synthetic oligosacchari de analog of SLX reduces allograft rejection and reperfusion injury by abrogation of P-selectin-dependent leukocyte-endothelial interaction. According to these findings, treatment with oligosaccharides to reduc e reperfusion injury and rejection seems to be a promising strategy fo r clinical lung transplantation.