Identification and characterization of an active soluble form of human CD38 in normal and pathological fluids

Human CD38 is a transmembrane glycoprotein involved in lymphocyte activation and adhesion to endothellum. The ectocellular domain of the molecule posessrs properties of a bifunctional enzyme catazying both the synthesis from NAD+ and the hydrolysis of the calcium-reteasing metabolote cyclic ADP-ribose (cADPSR). Surface expression of CD38(MCd38) is rapidly and almost completely down-modulated upon ligation by specific mAb in cells from different lineages. The data presented here also show that, in addition to the existence of a mCD38, a solubform of CD38 {aCD38}is detectable in the cell culture supernatant of allo-activated T hymphocytes and of several tumor cell lines,aCD38 is also present in vivo and is assayable in normal (fetal setrum and several fluid) and pathloogical (serum and ascities from patients with multiple myeloma, and serum from patients with AIDS) biological fluids. Immunoaffinity chromatography. SDS-PAGEb and Western blot analyses with mAb and polyclonal antibodies, along with metabolic labelling, yield a body of data concerning the structure of sCD38, which displaya a M, of 39 kDa. Native sCD38 maintains the ability to inhibit the binding activity of different anti-CD8mAb and still catalyzes the synthesis and the hydrolysis of cADPR at the same ratio observed with inCD38. Furthermore,cross-linking experiments indicate that the purified aoluble molecule binds a 120 kDa molecule expressed by monocytoid cells and identified as a candidate ligend for human mCD38.