title: Effect of oligosaccharides on rejection and reperfusion injury after lung transplantation.
abstract: 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.
authors.affiliation: Department of Cardiovascular Surgery, Christian-Albrechts-University, Kiel, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Brandt
authors.forename: K
authors.initials: K
authors.lastname: Boeke
authors.forename: M L
authors.initials: ML
authors.lastname: Phillips
authors.forename: G
authors.initials: G
authors.lastname: Steinhoff
authors.forename: A
authors.initials: A
authors.lastname: Haverich
mesh_terms: 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
chemical_list: D009844:Oligosaccharides; D019007:P-Selectin; D000080506:Sialyl Lewis X Antigen