Brandt M, Boeke K, Phillips M L, Steinhoff G, Haverich A
Department of Cardiovascular Surgery, Christian-Albrechts-University, Kiel, Germany.
J Heart Lung Transplant. 1997 Mar;16(3):352-9.
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.
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.
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.
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.
在排斥反应和再灌注损伤过程中，白细胞向肺移植组织的浸润受黏附分子调控，尤其是选择素。唾液酸化路易斯X（SLX）是一种寡糖，是P选择素黏附受体的膜配体分子。在本研究中，我们探讨了静脉注射SLX的合成寡糖类似物对大鼠肺移植后排斥反应和再灌注损伤的影响。
在平均总缺血时间为45分钟后，于完全不相容的大鼠品系（黑褐大鼠→刘易斯大鼠）之间进行左外侧原位同种异体肺移植。A组（n = 6）作为对照，未使用免疫抑制。在B组（n = 6）中，大鼠在第0至4天静脉注射200微克/千克/天的SLX。动物分别在第5天和第10天处死。在C组和D组中，进行同基因肺移植（刘易斯大鼠→刘易斯大鼠），缺血时间为7小时。C组（n = 6）作为未处理对照。D组大鼠（n = 6）在缺血结束时接受单次剂量20毫克/千克的SLX。动物分别在第2天和第5天处死。
在接受排斥反应治疗的B组大鼠中，组织学检查发现排斥反应程度较低（2.7±0.6对4.0±0.0，p<0.05），浸润的CD11a阳性白细胞较少（6.6±2.7对18.6±7.3，p<0.05）。在接受再灌注损伤治疗的D组大鼠中，胸部X线片和组织学研究均检测到再灌注损伤显著减轻。
SLX的合成寡糖类似物通过消除P选择素依赖性白细胞与内皮细胞的相互作用，减轻同种异体移植排斥反应和再灌注损伤。根据这些发现，用寡糖治疗以减轻再灌注损伤和排斥反应似乎是临床肺移植的一种有前景的策略。
