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 acti vation and adhesion to endothelium, The ectocellular domain of the mol ecule possesses properties of a bifunctional enzyme catalyzing both th e synthesis from NAD(+) and the hydrolysis of the calcium-releasing me tabolite cyclic ADP-ribose (cADPR), Surface expression of CD38 (mCD38) is rapidly and almost completely down-modulated upon ligation by spec ific mAb in cells from different lineages, The data presented here als o show that, in addition to the existence of a mCD38, a soluble form o f CD38 (sCD38) is detectable in the cell culture supernatant of allo-a ctivated T lymphocytes and of several tumor cell lines. sCD38 is also present in vivo and is assayable in normal (fetal serum and amniotic f luid) and pathological (serum and ascites from patients with multiple myeloma, and serum from patients with AIDS) biological fluids, Immunoa ffinity chromatography, SDS-PAGE and Western blot analyses with mAb an d polyclonal antibodies, along with metabolic labeling, yield a body o f data concerning the structure of sCD38, which displays a M(r) of 39 kDa, Native sCD38 maintains the ability to inhibit the binding activit y of different anti-CD38 mAb and still catalyzes the synthesis and the hydrolysis of cADPR at the same ratio observed with mCD38. Furthermor e, cross-linking experiments indicate that the purified soluble molecu le binds a 120 kDa molecule expressed by monocytoid cells and identifi ed as a candidate ligand for human mCD38.