Identification of alpha(v)beta(3) as a heterotypic ligand for CD31/PECAM-1

CD31 (PECAM-1) is a member of the immunoglobulin gene superfamily (IgSF) and has an important role in a number of endothelial cell functions including angiogenesis, inflammation, integrin activation and cell-cell adhesion. CD31 has both homotypic and heterotypic adhesive properties and in common with other IgSF members contains multiple functional domains, Using chimaeric fusion proteins of CD31 and a panel of haematopoietic cell lines we show that CD31 can bind cells in a predominantly homotypic or heterotypic manner depending on the cell line used, Heterotypic binding was found to be cation and temperature dependent and enhanced by Mn2+: all features of integrin mediated binding. Using a panel of anti-CD31 and anti-integrin antibodies we show that alpha(v) beta(3) is a ligand for CD31 on the monocytic cell line U937, The specificity of the interaction between alpha(v) beta(3) and CD31 was further confirmed by solid phase binding assays and the use of ccvPJ transfected cells which bound CD31 specifically. Furthermore, we have mapped the binding site for alpha(v) beta(3) to domains 1. and 2 of CD31, The interaction of CD31 with alpha(v) beta(3) may be important in many aspects of endothelial function including leukocyte-endothelial transmigration and angiogenesis.