NAD degradation and regulation of CD38 expression by human monocytes/macrophages

In recent years, evidence has accumulated that NAD(+) serves as a precursor of metabolites that are involved in a number of regulatory processes. In t his work we show that extracellularly added NAD(+) was rapidly degraded by intact human monocytes to nicotinamide and ADP-ribose. Besides these main p roducts, minor amounts of AMP, ADP and cADP-ribose were formed. Expression of CD38, which has been identified as NAD(+)-glycohydrolase (EC 3.2.2.6) de grading NAD(+) into nicotinamide and ADP-ribose, was determined on freshly isolated human monocytes by flow cytometry and RT-PCR. Upon ligation with a nti-CD38 mAb, CD38 underwent internalization, shedding and new expression. As monocytes possess an intracellular CD38 pool, it could serve as a source for newly expressed CD38. Differentiation of monocytes to macrophages resu lted in down-regulation of surface expression of CD38. This decrease correl ates with a reduction in NADase activity, indicating that the amount of fun ctional active CD38 molecules decrease during differentiation. As CD38 mRNA was found to be diminished in macrophages, regulation of the gene product seems to occur at the level of transcription or mRNA stability.