Objective: 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. Methods: 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 125I-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 125I-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. Results: 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. Conclusions: These results suggest that one potential mechanism of lung reperfusion injury involves the cleavage of E-cadherin.
- Ectodomain shedding
- Lung transplantation
- Reperfusion injury
- Soluble form
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Pulmonary and Respiratory Medicine