Effect of oligosaccharides on rejection and reperfusion injury after lung transplantation.
BACKGROUND
During rejection and reperfusion injury, infiltration of leukocytes into the lung allograft is regulated by adhesion molecules, especially selectins. Sialyl-Lewis X (SLX), an oligosaccharide, is a membrane ligand molecule of P-selectin adhesion receptors. In this study, we investigated the effect of intravenous administration of a synthetic oligosaccharide analog of SLX on rejection and reperfusion injury after rat lung transplantation.


METHODS
Left lateral, orthotopic, allogeneic lung transplantation was performed between fully incompatible rat strains (Dark Agouti-->Lewis) after an average total ischemic time of 45 minutes. Group A (n = 6) served as control; no immunosuppression was used. In group B (n = 6), rats received 200 micrograms/kg/day SLX intravenously on days 0 to 4. The animals were killed on days 5 and 10, respectively. In groups C and D, syngeneic lung transplantation was performed (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 animals 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 compared with group A. In group D rats, treated for reperfusion injury, a significant reduction of reperfusion injury was detected on chest radiograms and by histologic study.


CONCLUSIONS
A synthetic oligosaccharide 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 reduce reperfusion injury and rejection seems to be a promising strategy for clinical lung transplantation.
Brandt
M
M
Department of Cardiovascular Surgery, Christian-Albrechts-University, Kiel, Germany.
Boeke
K
K
Phillips
M L
ML
Steinhoff
G
G
Haverich
A
A
D000818:Animals; D006084:Graft Rejection / Q000473:pathology*; D008168:Lung / Q000098:blood supply / Q000473:pathology; D016040:Lung Transplantation / Q000473:pathology*; D008297:Male; D008833:Microcirculation / Q000473:pathology; D009844:Oligosaccharides / Q000494:pharmacology*; D019007:P-Selectin / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000473:pathology*; D000080506:Sialyl Lewis X Antigen
D009844:Oligosaccharides; D019007:P-Selectin; D000080506:Sialyl Lewis X Antigen