HUMAN CD38 (ADP-RIBOSYL CYCLASE) IS A COUNTER-RECEPTOR OF CD31, AN IGSUPERFAMILY MEMBER

Human CD38 is a cell surface molecule involved in the regulation of ly mphocyte adhesion to endothelial cells, This suggests that HUVEC bear a ligand(s) for CD38 on the cell surface, By means of the mAb Moon-1, which specifically inhibits CD38-mediated cell adhesion, we have ident ified a trans-membrane 130-kDa molecule acting as a ligand for CD38, H ere, we report that the molecule recognized by the Moon-1 mAb is CD31, a member of the Ig superfamily, This conclusion is based on 1) cross- inhibition assays between Moon-1 and reference anti-CD31 mAbs; 2) sequ ential immunoprecipitation experiments using Moon-1 and known anti-CD3 1 mAbs, and 3) reactivity of the Moon-1 mAb with CD31 transfectants, F urther, CD31 and CD38 cognate interactions were found to modulate hete rotypic adhesion as well as to implement cytoplasmic calcium fluxes id entical to those obtained by means of agonistic anti-CD38 mAbs. Other effects tested included the synthesis of messages for a panel of cytok ines, markedly increased upon receptor-ligand interactions. These resu lts suggest that the interplay between CD38 and its ligand CD31 is an important step in the regulation of cell life and of the migration of leukocytes (and CD38(+) cancer cells) through the endothelial cell wal l.