Title
Nicotinamide adenine dinucleotide (NAD) and its metabolites inhibit T lymphocyte proliferation: role of cell surface NAD glycohydrolase and pyrophosphatase activities
GSBS Program
Biochemistry & Molecular Pharmacology
Publication Date
2001-08-08
UMMS Affiliation
Graduate School of Biomedical Sciences; Department of Medicine, Diabetes Division; Department of Medicine, Division of Endocrinology and Metabolism
Document Type
Article
Disciplines
Life Sciences | Medicine and Health Sciences
Abstract
The presence of NAD-metabolizing enzymes (e.g., ADP-ribosyltransferase (ART)2) on the surface of immune cells suggests a potential immunomodulatory activity for ecto-NAD or its metabolites at sites of inflammation and cell lysis where extracellular levels of NAD may be high. In vitro, NAD inhibits mitogen-stimulated rat T cell proliferation. To investigate the mechanism of inhibition, the effects of NAD and its metabolites on T cell proliferation were studied using ART2a+ and ART2b+ rat T cells. NAD and ADP-ribose, but not nicotinamide, inhibited proliferation of mitogen-activated T cells independent of ART2 allele-specific expression. Inhibition by P2 purinergic receptor agonists was comparable to that induced by NAD and ADP-ribose; these compounds were more potent than P1 agonists. Analysis of the NAD-metabolizing activity of intact rat T cells demonstrated that ADP-ribose was the predominant metabolite, consistent with the presence of cell surface NAD glycohydrolase (NADase) activities. Treatment of T cells with phosphatidylinositol-specific phospholipase C removed much of the NADase activity, consistent with at least one NADase having a GPI anchor; ART2- T cell subsets contained NADase activity that was not releasable by phosphatidylinositol-specific phospholipase C treatment. Formation of AMP from NAD and ADP-ribose also occurred, a result of cell surface pyrophosphatase activity. Because AMP and its metabolite, adenosine, were less inhibitory to rat T cell proliferation than was NAD or ADP-ribose, pyrophosphatases may serve a regulatory role in modifying the inhibitory effect of ecto-NAD on T cell activation. These data suggest that T cells express multiple NAD and adenine nucleotide-metabolizing activities that together modulate immune function.
DOI of Published Version
10.4049/jimmunol.167.4.2049
Source
J Immunol. 2001 Aug 15;167(4):2049-59.
Journal/Book/Conference Title
Journal of immunology (Baltimore, Md. : 1950)
Related Resources
PubMed ID
11489987
Repository Citation
Bortell R, Moss J, McKenna RC, Rigby MR, Niedzwiecki D, Stevens LA, Patton WA, Mordes JP, Greiner DL, Rossini AA. (2001). Nicotinamide adenine dinucleotide (NAD) and its metabolites inhibit T lymphocyte proliferation: role of cell surface NAD glycohydrolase and pyrophosphatase activities. GSBS Student Publications. https://doi.org/10.4049/jimmunol.167.4.2049. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/111