Novel α4-integrin ligands on an endothelial cell line

The unique combination of adhesion molecules expressed on endothelial cells is thought to mediate the specificity of leukocyte-endothelial cell interactions. In this study, murine endothelial cell lines were used as a model to identify novel adhesion molecules that participate in these cellular interactions. Lymphocyte adhesion to the continuous endothelial cell lines mHEVa and mHEVc required α4-integrin. Interestingly, lymphocyte α4-integrin bound to VCAM-1 as well as an unknown ligand on the mHEVa cell line. We have demonstrated that this VCAM-1-independent adhesion to the mHEVa cells was not mediated by other known α4-integrin ligands (fibronectin, α4-integrin itself, or MAdCAM-1). Two novel α4-integrin ligands (p50 and p10) were isolated from the mHEVa cell line but not the mHEVc cell line by B cell α4- integrin-specific ligand binding of radiolabeled mHEV cell membrane proteins. These results provide the first direct evidence that novel ligands for α4- integrin exist on membranes from endothelial cells.