This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ohlrogge, W.
Right arrow Articles by Koch-Nolte, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ohlrogge, W.
Right arrow Articles by Koch-Nolte, F.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, November 2002, p. 7535-7542, Vol. 22, No. 21
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.21.7535-7542.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Generation and Characterization of Ecto-ADP-Ribosyltransferase ART2.1/ART2.2-Deficient Mice

Wiebke Ohlrogge,1 Friedrich Haag,1,{dagger} Jürgen Löhler,2 Michel Seman,3 Dan R. Littman,4,5 Nigel Killeen,5 and Friedrich Koch-Nolte1*

Institute of Immunology,1 Heinrich Pette Institute, University Hospital, Hamburg 20246, Germany,2 Université Denis Diderot, Paris 75251, France,3 Howard Hughes Medical Institute, Skirball Institute, New York, New York 10016,4 Department of Microbiology, University of California, San Francisco, California 941435

Received 9 May 2002/ Returned for modification 2 July 2002/ Accepted 8 August 2002

This is the first study reporting the inactivation of a member of the mouse gene family of toxin-related ecto-ADP-ribosyltransferases (ARTs). Transfer of the ADP-ribose moiety from NAD onto extracellular arginine residues on T-cell membrane proteins is mediated by glycosylphosphatidylinositol-linked cell surface ARTs. Exposure of T cells to ecto-NAD blocks T-cell activation and induces T-cell apoptosis. To determine a possible role of ecto-ART2.1 and ART2.2 in these processes, we generated ART2.1/ART2.2 double-knockout mice. ART2-deficient mice were healthy and fertile and showed normal development of lymphoid organs. ART2-deficient T cells showed a dramatically reduced capacity to ADP-ribosylate cell surface proteins, indicating that most if not all ART activity on the T-cell surface can be attributed to the ART2s. Moreover, ART2-deficient T cells were completely resistant to NAD-induced apoptosis and partially resistant to NAD-mediated suppression of proliferation. These results demonstrate that the ART2 ectoenzymes are an essential component in the regulation of T-cell functions by extracellular NAD, e.g., following release of NAD upon lysis of cells in tissue injury and inflammation.

* Corresponding author. Mailing address: Institute of Immunology, University Hospital, D20246 Hamburg, Germany. Phone: 49/40/42803 3612. Fax: 49/40/42803 4243. E-mail: nolte{at}uke.uni-hamburg.de.

{dagger} Present address: Vaccinelab, Rostock, Germany.

Molecular and Cellular Biology, November 2002, p. 7535-7542, Vol. 22, No. 21
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.21.7535-7542.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Hong, S., Schwarz, N., Brass, A., Seman, M., Haag, F., Koch-Nolte, F., Schilling, W. P., Dubyak, G. R. (2009). Differential Regulation of P2X7 Receptor Activation by Extracellular Nicotinamide Adenine Dinucleotide and Ecto-ADP-Ribosyltransferases in Murine Macrophages and T Cells. J. Immunol. 183: 578-592 [Abstract] [Full Text]  
  • Scheuplein, F., Schwarz, N., Adriouch, S., Krebs, C., Bannas, P., Rissiek, B., Seman, M., Haag, F., Koch-Nolte, F. (2009). NAD+ and ATP Released from Injured Cells Induce P2X7-Dependent Shedding of CD62L and Externalization of Phosphatidylserine by Murine T Cells. J. Immunol. 182: 2898-2908 [Abstract] [Full Text]  
  • Heiss, K., Janner, N., Mahnss, B., Schumacher, V., Koch-Nolte, F., Haag, F., Mittrucker, H.-W. (2008). High Sensitivity of Intestinal CD8+ T Cells to Nucleotides Indicates P2X7 as a Regulator for Intestinal T Cell Responses. J. Immunol. 181: 3861-3869 [Abstract] [Full Text]  
  • Hong, S., Brass, A., Seman, M., Haag, F., Koch-Nolte, F., Dubyak, G. R. (2007). Lipopolysaccharide, IFN-{gamma}, and IFN-beta Induce Expression of the Thiol-Sensitive ART2.1 Ecto-ADP-Ribosyltransferase in Murine Macrophages. J. Immunol. 179: 6215-6227 [Abstract] [Full Text]  
  • Adriouch, S., Hubert, S., Pechberty, S., Koch-Nolte, F., Haag, F., Seman, M. (2007). NAD+ Released during Inflammation Participates in T Cell Homeostasis by Inducing ART2-Mediated Death of Naive T Cells In Vivo. J. Immunol. 179: 186-194 [Abstract] [Full Text]  
  • Hassa, P. O., Haenni, S. S., Elser, M., Hottiger, M. O. (2006). Nuclear ADP-Ribosylation Reactions in Mammalian Cells: Where Are We Today and Where Are We Going?. Microbiol. Mol. Biol. Rev. 70: 789-829 [Abstract] [Full Text]  
  • Chen, J., Chen, Y.-G., Reifsnyder, P. C., Schott, W. H., Lee, C.-H., Osborne, M., Scheuplein, F., Haag, F., Koch-Nolte, F., Serreze, D. V., Leiter, E. H. (2006). Targeted Disruption of CD38 Accelerates Autoimmune Diabetes in NOD/Lt Mice by Enhancing Autoimmunity in an ADP-Ribosyltransferase 2-Dependent Fashion.. J. Immunol. 176: 4590-4599 [Abstract] [Full Text]  
  • Kawamura, H., Aswad, F., Minagawa, M., Govindarajan, S., Dennert, G. (2006). P2X7 Receptors Regulate NKT Cells in Autoimmune Hepatitis. J. Immunol. 176: 2152-2160 [Abstract] [Full Text]  
  • Carlo-Stella, C., Di Nicola, M., Turco, M. C., Cleris, L., Lavazza, C., Longoni, P., Milanesi, M., Magni, M., Ammirante, M., Leone, A., Nagy, Z., Gioffre, W. R., Formelli, F., Gianni, A. M. (2006). The Anti-Human Leukocyte Antigen-DR Monoclonal Antibody 1D09C3 Activates the Mitochondrial Cell Death Pathway and Exerts a Potent Antitumor Activity in Lymphoma-Bearing Nonobese Diabetic/Severe Combined Immunodeficient Mice. Cancer Res. 66: 1799-1808 [Abstract] [Full Text]  
  • Krebs, C., Adriouch, S., Braasch, F., Koestner, W., Leiter, E. H., Seman, M., Lund, F. E., Oppenheimer, N., Haag, F., Koch-Nolte, F. (2005). CD38 Controls ADP-Ribosyltransferase-2-Catalyzed ADP-Ribosylation of T Cell Surface Proteins. J. Immunol. 174: 3298-3305 [Abstract] [Full Text]  
  • Kawamura, H., Aswad, F., Minagawa, M., Malone, K., Kaslow, H., Koch-Nolte, F., Schott, W. H., Leiter, E. H., Dennert, G. (2005). P2X7 Receptor-Dependent and -Independent T Cell Death Is Induced by Nicotinamide Adenine Dinucleotide. J. Immunol. 174: 1971-1979 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»