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 (IgS F) and has an important role in a number of endothelial cell functions including angiogenesis, inflammation, integrin activation and cell-ce ll adhesion. CD31 has both homotypic and heterotypic adhesive properti es and in common with other IgSF members contains multiple functional domains, Using chimaeric fusion proteins of CD31 and a panel of haemat opoietic cell lines we show that CD31 can bind cells in a predominantl y homotypic or heterotypic manner depending on the cell line used, Het erotypic binding was found to be cation and temperature dependent and enhanced by Mn2+: all features of integrin mediated binding. Using a p anel of anti-CD31 and anti-integrin antibodies we show that alpha(v) b eta(3) is a ligand for CD31 on the monocytic cell line U937, The speci ficity of the interaction between alpha(v) beta(3) and CD31 was furthe r confirmed by solid phase binding assays and the use of ccvPJ transfe cted 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 as pects of endothelial function including leukocyte-endothelial transmig ration and angiogenesis.