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dc.contributor.authorBortell, Rita
dc.contributor.authorMoss, Joel
dc.contributor.authorMcKenna, Robert C.
dc.contributor.authorRigby, Mark R.
dc.contributor.authorNiedzwiecki, Dena
dc.contributor.authorStevens, Linda A.
dc.contributor.authorPatton, Walter A.
dc.contributor.authorMordes, John P.
dc.contributor.authorGreiner, Dale L.
dc.contributor.authorRossini, Aldo A.
dc.date2022-08-11T08:08:48.000
dc.date.accessioned2022-08-23T16:08:50Z
dc.date.available2022-08-23T16:08:50Z
dc.date.issued2001-08-08
dc.date.submitted2008-08-05
dc.identifier.citation<p>J Immunol. 2001 Aug 15;167(4):2049-59.</p>
dc.identifier.issn0022-1767 (Print)
dc.identifier.doi10.4049/jimmunol.167.4.2049
dc.identifier.pmid11489987
dc.identifier.urihttp://hdl.handle.net/20.500.14038/32545
dc.description.abstractThe 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.isoen_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.urlhttps://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.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleNicotinamide adenine dinucleotide (NAD) and its metabolites inhibit T lymphocyte proliferation: role of cell surface NAD glycohydrolase and pyrophosphatase activities
dc.typeJournal Article
dc.source.journaltitleJournal of immunology (Baltimore, Md. : 1950)
dc.source.volume167
dc.source.issue4
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_sp/111
dc.identifier.contextkey566365
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.submissionpathgsbs_sp/111
dc.contributor.departmentDepartment of Medicine, Division of Endocrinology and Metabolism
dc.contributor.departmentDepartment of Medicine, Diabetes Division
dc.contributor.departmentGraduate School of Biomedical Sciences
dc.source.pages2049-59


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