Nicotinamide adenine dinucleotide (NAD) and its metabolites inhibit T lymphocyte proliferation: role of cell surface NAD glycohydrolase and pyrophosphatase activities
Authors
Bortell, RitaMoss, Joel
McKenna, Robert C.
Rigby, Mark R.
Niedzwiecki, Dena
Stevens, Linda A.
Patton, Walter A.
Mordes, John P.
Greiner, Dale L.
Rossini, Aldo A.
UMass Chan Affiliations
Department of Medicine, Division of Endocrinology and MetabolismDepartment of Medicine, Diabetes Division
Graduate School of Biomedical Sciences
Document Type
Journal ArticlePublication Date
2001-08-08Keywords
*ADP Ribose Transferases; Adenosine; Adenosine Diphosphate; Adenosine Diphosphate Ribose; Adenosine Monophosphate; Animals; Antigens, Differentiation, T-Lymphocyte; Cell Membrane; Cells, Cultured; Cholera Toxin; Female; Histocompatibility Antigens; Immunosuppressive Agents; *Lymphocyte Activation; Male; *Membrane Glycoproteins; Mitogens; NAD; NAD+ Nucleosidase; Pertussis Toxin; Phosphatidylinositol Diacylglycerol-Lyase; Phosphoinositide Phospholipase C; Phosphorus Radioisotopes; Poly(ADP-ribose) Polymerases; Pyrophosphatases; Rats; Rats, Inbred BB; Rats, Inbred WF; T-Lymphocytes; Type C Phospholipases; Virulence Factors, BordetellaLife Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
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.Source
J Immunol. 2001 Aug 15;167(4):2049-59.
DOI
10.4049/jimmunol.167.4.2049Permanent Link to this Item
http://hdl.handle.net/20.500.14038/32545PubMed ID
11489987Related Resources
ae974a485f413a2113503eed53cd6c53
10.4049/jimmunol.167.4.2049