Funaro A, Horenstein A L, Calosso L, Morra M, Tarocco R P, Franco L, De Flora A, Malavasi F
Department of Genetics, Biology and Medical Chemistry, University of Turin, Italy.
Int Immunol. 1996 Nov;8(11):1643-50. doi: 10.1093/intimm/8.11.1643.
Human CD38 is a transmembrane glycoprotein involved in lymphocyte activation and adhesion to endothelium. The ectocellular domain of the molecule possesses properties of a bifunctional enzyme catalyzing both the synthesis from NAD+ and the hydrolysis of the calcium-releasing metabolite cyclic ADP-ribose (cADPR). 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 soluble form of CD38 (sCD38) is detectable in the cell culture supernatant of allo-activated T lymphocytes and of several tumor cell lines. sCD38 is also present in vivo and is assayable in normal (fetal serum and amniotic fluid) and pathological (serum and ascites from patients with multiple myeloma, and serum from patients with AIDS) biological fluids. Immunoaffinity chromatography, SDS-PAGE and Western blot analyses with mAb and polyclonal antibodies, along with metabolic labeling, yield a body of data concerning the structure of sCD38, which displays a M(r) of 39 kDa. Native sCD38 maintains the ability to inhibit the binding activity of different anti-CD38 mAb and still catalyzes the synthesis and the hydrolysis of cADPR at the same ratio observed with mCD38. Furthermore, cross-linking experiments indicate that the purified soluble molecule binds a 120 kDa molecule expressed by monocytoid cells and identified as a candidate ligand for human mCD38.
人类CD38是一种跨膜糖蛋白，参与淋巴细胞活化以及与内皮细胞的黏附。该分子的胞外结构域具有双功能酶的特性，既能催化由NAD⁺合成，又能催化钙释放代谢物环ADP核糖（cADPR）的水解。在不同谱系的细胞中，特异性单克隆抗体（mAb）结合后，CD38（mCD38）的表面表达会迅速且几乎完全下调。本文提供的数据还表明，除了存在mCD38外，在同种异体激活的T淋巴细胞和几种肿瘤细胞系的细胞培养上清液中可检测到可溶性形式的CD38（sCD38）。sCD38在体内也存在，并且可在正常（胎儿血清和羊水）和病理（多发性骨髓瘤患者的血清和腹水，以及艾滋病患者的血清）生物体液中检测到。使用mAb和多克隆抗体进行免疫亲和色谱、SDS-PAGE和蛋白质印迹分析，以及代谢标记，产生了一系列关于sCD38结构的数据，其分子量（M(r)）为39 kDa。天然sCD38保持抑制不同抗CD38 mAb结合活性的能力，并且仍以与mCD38相同的比例催化cADPR的合成和水解。此外，交联实验表明，纯化的可溶性分子与单核细胞样细胞表达的120 kDa分子结合，该分子被鉴定为人类mCD38的候选配体。
