Department of General Thoracic Surgery, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.
Eur J Cardiothorac Surg. 2010 Feb;37(2):426-31. doi: 10.1016/j.ejcts.2009.06.041. Epub 2009 Jul 29.
E-cadherin is a major cell-to-cell adhesion molecule, of which the ectodomain is cleaved from epithelial cells to yield a soluble form after the pathological alteration of the alveolar epithelium. We investigated the excretion level of soluble E-cadherin in a rat lung isotransplant model, and demonstrated the involvement of this molecule in the pathogenesis of reperfusion injury after lung transplantation.
Inbred male Lewis rats were used as both donor and recipient animals, and they were subjected to left lung isotransplantation. After 6 h of ischaemia, the left lung was transplanted into a recipient rat and reperfused for 4 h. The animals were injected intravenously with (125)I-labelled albumin at 3 h after the onset of reperfusion as a marker of pulmonary albumin leakage. We assessed pulmonary alveolar septal damage quantitatively based on the (125)I-albumin concentration ratio of bronchoalveolar lavage fluid (BALF) to plasma. Soluble E-cadherin fragments were detected in BALF on Western blot analysis using affinity-purified antibodies specific to rat E-cadherin synthetic peptides.
The BALF supernatant-to-plasma ratio of the graft lung was significantly increased compared to that of the control group. Western blot analysis showed a marked release of soluble E-cadherin into BALF, and its increase in BALF was associated with alveolar septal damage.
These results suggest that one potential mechanism of lung reperfusion injury involves the cleavage of E-cadherin.
E-钙黏蛋白是一种主要的细胞间黏附分子，其细胞外结构域在肺泡上皮发生病理性改变后从上皮细胞中被切割下来，产生可溶性形式。我们在大鼠肺同种异体移植模型中研究了可溶性 E-钙黏蛋白的排泄水平，并证明了该分子参与了肺移植后再灌注损伤的发病机制。
近交系雄性 Lewis 大鼠被用作供体和受体动物，并进行左肺同种异体移植。缺血 6 小时后，将左肺移植到受体大鼠体内，并再灌注 4 小时。在再灌注开始后 3 小时，动物静脉注射 (125)I 标记的白蛋白作为肺白蛋白渗漏的标志物。我们根据支气管肺泡灌洗液 (BALF)与血浆中 (125)I-白蛋白浓度比，对肺肺泡间隔损伤进行定量评估。通过使用针对大鼠 E-钙黏蛋白合成肽的亲和纯化抗体的 Western blot 分析，在 BALF 中检测到可溶性 E-钙黏蛋白片段。
与对照组相比，移植物肺的 BALF 上清液/血浆比值显著增加。Western blot 分析显示，可溶性 E-钙黏蛋白明显释放到 BALF 中，其在 BALF 中的增加与肺泡间隔损伤有关。
这些结果表明，肺再灌注损伤的一个潜在机制涉及 E-钙黏蛋白的切割。
