Nicotinamide adenine dinucleotide (NAD) and its metabolites inhibit T lymphocyte proliferation: role of cell surface NAD glycohydrolase and pyrophosphatase activities.

摘要: The presence of NAD-metabolizing enzymes (e.g., ADP-ribosyltransferase (ART)2) on the surface immune cells suggests a potential immunomodulatory activity for ecto-NAD or its metabolites at sites inflammation and cell lysis where extracellular levels NAD may be high. In vitro, inhibits mitogen-stimulated rat T proliferation. To investigate mechanism inhibition, effects proliferation were studied using ART2a+ ART2b+ cells. ADP-ribose, but not nicotinamide, inhibited mitogen-activated independent ART2 allele-specific expression. Inhibition by P2 purinergic receptor agonists was comparable to that induced ADP-ribose; these compounds more potent than P1 agonists. Analysis intact demonstrated ADP-ribose predominant metabolite, consistent with glycohydrolase (NADase) activities. Treatment phosphatidylinositol-specific phospholipase C removed much NADase activity, least one having GPI anchor; ART2− subsets contained releasable treatment. Formation AMP from also occurred, result pyrophosphatase activity. Because adenosine, less inhibitory pyrophosphatases serve regulatory role in modifying effect activation. These data suggest express multiple adenine nucleotide-metabolizing activities together modulate function.