These results demonstrate that an early interaction between allogeneic blood lymphocytes and vascular endothelial cells is correlated with a high mRNA expression both of adhesion molecules and of TNF-alpha in the perfused lung. Our model of a mouse lung perfused with fresh blood appears to be a useful clinical assessment system for in-depth investigation of early cell activation and the resulting intragraft immune alterations.

Altogether, our results demonstrate that E-selectin expression (1) is not a consequence of TNF-alpha triggering, (2) up-regulates its own expression and expression of I-A, VCAM-1, TNF-alpha, and lymphotoxin-alpha mRNAs, and (3) down-regulates expression of LFA-3 and ICAM-1 mRNAs. In conclusion, in our physiologic model, the E-selectin highly participates in the loose adhesion of allogeneic lymphocytes and in the early activation of endothelial cell and therefore in structural and functional lung alterations.

In our model, the engagement of E-selectin induced by endothelial cell allogeneic activation appeared to be a prerequisite for lung apoptosis, which involved FasL and increase of PTP activity. Blockade of apoptosis with selective inhibitors may be a promising approach to the treatment/prevention of lung graft injury.