Involvement of E-cadherin cleavage in reperfusion injury.
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 (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.


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.
Goto
Taichiro
T
Department of General Thoracic Surgery, National Hospital Organization Tokyo Medical Center, Tokyo, Japan. tgoto@ntmc.hosp.go.jp
Ishizaka
Akitoshi
A
Katayama
Masahiko
M
Kohno
Mitsutomo
M
Tasaka
Sadatomo
S
Fujishima
Seitaro
S
Kobayashi
Koichi
K
Nomori
Hiroaki
H
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D015820:Cadherins / Q000378:metabolism*; D007457:Iodine Radioisotopes; D016040:Lung Transplantation / Q000473:pathology; D008297:Male; D011654:Pulmonary Edema / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D012709:Serum Albumin
D015820:Cadherins; D007457:Iodine Radioisotopes; D012709:Serum Albumin