CD38 BINDING TO HUMAN MYELOID CELLS IS MEDIATED BY MOUSE AND HUMAN CD31

Soluble forms of membrane receptors are emerging candidates as physiol ogical regulators of leukocyte trafficking. In the present study, we f ound that the soluble form of the CD38 antigen (sCD38) bears a binding domain of low affinity for a cellular receptor on U937 cells, Cross-l inking and peptide-mapping studies confirmed the physical association and the identification of the U937 receptor as a 130 kDa protein. The binding of sCD38 to the receptor was differentially inhibited by sever al monoclonal antibodies against the CD31 cell-adhesion molecule. Thus the interaction was analysed through direct association of soluble an d membrane CD38 with soluble recombinant murine CD31 with three N-term inal and with all six extracellular Ig domains. Cross-linking experime nts on U937 intact cells, and ligand blot assays of the immunoprecipit ated CD38 molecule, indicated that (i) the recognized epitope is deter mined by the tertiary structure of the molecule, and that (ii) the bin ding domain involved resides in the ectocellular portion of the CD31 m olecule, more precisely in the first three N-terminal domains. A compa rative functional activity between murine and human CD31 was also expl ored. The data presented suggest that (i) human CD31 bears a highly fu nctional similarity with its murine counterpart, as it is a receptor i n myeloid cells with more than one ligand (the alpha(v) beta(3) integr in and the CD38 molecule), and that (ii) the activity of sCD38 as deco y molecule for CD31 may play an important role in cell-cell interactio ns in physiological and pathological conditions.