Nicotinamide adenine dinucleotide (NAD) and its metabolites inhibit T lymphocyte proliferation: role of cell surface NAD glycohydrolase and pyrophosphatase activities
dc.contributor.author | Bortell, Rita | |
dc.contributor.author | Moss, Joel | |
dc.contributor.author | McKenna, Robert C. | |
dc.contributor.author | Rigby, Mark R. | |
dc.contributor.author | Niedzwiecki, Dena | |
dc.contributor.author | Stevens, Linda A. | |
dc.contributor.author | Patton, Walter A. | |
dc.contributor.author | Mordes, John P. | |
dc.contributor.author | Greiner, Dale L. | |
dc.contributor.author | Rossini, Aldo A. | |
dc.date | 2022-08-11T08:08:48.000 | |
dc.date.accessioned | 2022-08-23T16:08:50Z | |
dc.date.available | 2022-08-23T16:08:50Z | |
dc.date.issued | 2001-08-08 | |
dc.date.submitted | 2008-08-05 | |
dc.identifier.citation | <p>J Immunol. 2001 Aug 15;167(4):2049-59.</p> | |
dc.identifier.issn | 0022-1767 (Print) | |
dc.identifier.doi | 10.4049/jimmunol.167.4.2049 | |
dc.identifier.pmid | 11489987 | |
dc.identifier.uri | http://hdl.handle.net/20.500.14038/32545 | |
dc.description.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. | |
dc.language.iso | en_US | |
dc.relation | <p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11489987&dopt=Abstract ">Link to article in PubMed</a></p> | |
dc.relation.url | https://doi.org/10.4049/jimmunol.167.4.2049 | |
dc.subject | *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, Bordetella | |
dc.subject | Life Sciences | |
dc.subject | Medicine and Health Sciences | |
dc.title | Nicotinamide adenine dinucleotide (NAD) and its metabolites inhibit T lymphocyte proliferation: role of cell surface NAD glycohydrolase and pyrophosphatase activities | |
dc.type | Journal Article | |
dc.source.journaltitle | Journal of immunology (Baltimore, Md. : 1950) | |
dc.source.volume | 167 | |
dc.source.issue | 4 | |
dc.identifier.legacycoverpage | https://escholarship.umassmed.edu/gsbs_sp/111 | |
dc.identifier.contextkey | 566365 | |
html.description.abstract | <p>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.</p> | |
dc.identifier.submissionpath | gsbs_sp/111 | |
dc.contributor.department | Department of Medicine, Division of Endocrinology and Metabolism | |
dc.contributor.department | Department of Medicine, Diabetes Division | |
dc.contributor.department | Graduate School of Biomedical Sciences | |
dc.source.pages | 2049-59 |