HUMAN CD38 LIGAND - A 120-KDA PROTEIN PREDOMINANTLY EXPRESSED ON ENDOTHELIAL-CELLS

Human CD38, a pleiotropic molecule with ADP-ribosyl cyclase activity, regulates activation and growth of several cell types, Its in vivo fun ction is incompletely determined, mainly due to the lack of evidence c oncerning the existence of a single or multiple ligands, We recently o bserved that CD38 rules a selectin-type adhesion between lymphoid cell s and HUVECs, A panel of murine mAbs raised against HUVEC included one (Moon-1) constantly blocking the CD38-mediated adhesion of several ce ll lines to HUVFC, Tissue distribution studies and an extended immunoh istochemical analysis on the majority of normal human tissues revealed that the Moon-1 molecule displays a unique pattern of expression, bei ng present at high levels on resting and activated vascular endotheliu m, on the majority of monocytes, platelets, NK cells, and to a lesser extent on T, B, and myeloid cells, The Moon-1 structure of an apparent molecular mass of 120 kDa proved to be a ligand for human CD38, as in ferred by the direct binding observed when using a chimeric mouseCD8 a lpha-humanCD38 (mCD8 alpha-hCD38) molecule as a probe in Western blot experiments, Furthermore, Ab-induced modulation experiments highlighte d an association between the Moon-1 molecule and human CD38 on the sur face of cell lines coexpressing the two structures, which also share a common regulation system of surface expression, Finally, direct ligat ion of Moon-1 on T cell lines caused a relevant increase in the cytopl asmic concentration of calcium ([Ca-2+](i)).