CD31 PECAM-1 IS A LIGAND FOR ALPHA(V)BETA(3) INTEGRIN INVOLVED IN ADHESION OF LEUKOCYTES TO ENDOTHELIUM/

To protect the body efficiently from infectious organisms, leukocytes circulate as nonadherent cells in the blood and lymph, and migrate as adherent cells into tissues. Circulating leukocytes in the blood have first to adhere to and then to cross the endothelial lining. CD31/PECA M-1 is an adhesion molecule expressed by vascular endothelial cells, p latelets, monocytes, neutrophils, and naive T lymphocytes. It is a tra nsmembrane glycoprotein of the immunoglobulin gene superfamily (IgSF), with six Ig-like homology units mediating leukocyte-endothelial inter actions. The adhesive interactions mediated by CD31 are complex and in clude hemophilic (CD31-CD31) or heterophilic (CD31-X) contacts. Solubl e, recombinant forms of CD31 allowed us to study the heterophilic inte ractions in leukocyte adhesion assays. We show that the adhesion molec ule alpha(v) beta(3) integrin is a ligand for CD31. The leukocytes rev ealed adhesion mediated by the second Ig-like domain of CD31, and this binding was inhibited by alpha(v) beta(3) integrin-specific antibodie s. Moreover alpha(v) beta(3) was precipitated by recombinant CD31 from cell lysates. These data establish a third IgSF-integrin pair of adhe sion molecules, CD31-alpha(v) beta(3) in addition to VCAM-1, MadCAM-1/ alpha 4 integrins, and ICAM/beta 2 integrins, which are major componen ts mediating leukocyte-endothelial adhesion. Identification of a furth er versatile adhesion pair broadens our current understanding of leuko cyte-endothelial interactions and may provide the basis for the treatm ent of inflammatory disorders and metastasis formation.