Novel alpha 4-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 intera ctions. In this study, murine endothelial cell lines were used as a model t o identify novel adhesion molecules that participate in these cellular inte ractions. Lymphocyte adhesion to the continuous endothelial cell lines mHEV a and mHEVc required alpha 4-integrin. Interestingly, lymphocyte alpha 4-in tegrin 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 ce lls was not mediated by other known alpha 4-integrin ligands (fibronectin, alpha 4-integrin itself, or MAdCAM-1). Two novel alpha 4-integrin ligands ( p50 and p10) were isolated from the mHEVa cell line but not the mHEVc cell line by B cell alpha 4-integrin-specific ligand binding of radiolabeled mHE V cell membrane proteins. These results provide the first direct evidence t hat novel ligands for alpha 4-integrin exist on membranes from endothelial cells.