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Blood, 1 September 2006, Vol. 108, No. 5, pp. 1627-1634. Prepublished online as a Blood First Edition Paper on May 18, 2006; DOI 10.1182/blood-2006-11-010389. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-11-010389v1 108/5/1627    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Munder, M. Articles by Ho, A. D. Search for Related Content PubMed PubMed Citation Articles by Munder, M. Articles by Ho, A. D. Related Collections Immunobiology Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Suppression of T-cell functions by human granulocyte arginase Markus Munder, Henriette Schneider, Claudia Luckner, Thomas Giese, Claus-Dieter Langhans, Jose M. Fuentes, Pascale Kropf, Ingrid Mueller, Armin Kolb, Manuel Modolell, and Anthony D. Ho From the Department of Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Germany; Institute of Immunology, University of Heidelberg, Germany; Children's Hospital, University of Heidelberg, Germany; Departamento de Bioquímica y Biología Molecular, E.U. Enfermería y T.O., Universidad de Extremadura, Cáceres, Spain; Department of Immunology, Faculty of Medicine, Imperial College London, United Kingdom; Department of Surgery, University Hospital Heidelberg, Germany; and Department of Cellular Immunology, Max-Planck-Institute for Immunobiology, Freiburg, Germany. Chronic inflammation is accompanied by impaired T-cell immunity. In the mouse, myeloid cell-associated arginase accounts for the suppression of immune reactivity in various models of tumor growth and chronic infections. Here we show that arginase I is liberated from human granulocytes, and very high activities accumulate extracellularly during purulent inflammatory reactions. Human granulocyte arginase induces a profound suppression of T-cell proliferation and cytokine synthesis. This T-cell phenotype is due to arginase-mediated depletion of arginine in the T-cell environment, which leads to CD3 chain down-regulation but does not alter T-cell viability. Our study therefore demonstrates that human granulocytes possess a previously unanticipated immunosuppressive effector function. Human granulocyte arginase is a promising pharmacologic target to reverse unwanted immunosuppression. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Q. Liu, C. Zhang, A. Sun, Y. Zheng, L. Wang, and X. Cao Tumor-Educated CD11bhighIalow Regulatory Dendritic Cells Suppress T Cell Response through Arginase I J. Immunol., May 15, 2009; 182(10): 6207 - 6216. [Abstract] [Full Text] [PDF] S. Mandruzzato, S. Solito, E. Falisi, S. Francescato, V. Chiarion-Sileni, S. Mocellin, A. Zanon, C. R. Rossi, D. Nitti, V. Bronte, et al. IL4R{alpha}+ Myeloid-Derived Suppressor Cell Expansion in Cancer Patients J. Immunol., May 15, 2009; 182(10): 6562 - 6568. [Abstract] [Full Text] [PDF] J. Oberlies, C. Watzl, T. Giese, C. Luckner, P. Kropf, I. Muller, A. D. Ho, and M. Munder Regulation of NK Cell Function by Human Granulocyte Arginase J. Immunol., May 1, 2009; 182(9): 5259 - 5267. [Abstract] [Full Text] [PDF] K. J. Mylonas, M. G. Nair, L. Prieto-Lafuente, D. Paape, and J. E. Allen Alternatively Activated Macrophages Elicited by Helminth Infection Can Be Reprogrammed to Enable Microbial Killing J. Immunol., March 1, 2009; 182(5): 3084 - 3094. [Abstract] [Full Text] [PDF] B.-S. Choi, I. C. Martinez-Falero, C. Corset, M. Munder, M. Modolell, I. Muller, and P. Kropf Differential impact of L-arginine deprivation on the activation and effector functions of T cells and macrophages J. Leukoc. Biol., February 1, 2009; 85(2): 268 - 277. [Abstract] [Full Text] [PDF] K. Kitowska, D. Zakrzewicz, M. Konigshoff, I. Chrobak, F. Grimminger, W. Seeger, P. Bulau, and O. Eickelberg Functional role and species-specific contribution of arginases in pulmonary fibrosis Am J Physiol Lung Cell Mol Physiol, January 1, 2008; 294(1): L34 - L45. [Abstract] [Full Text] [PDF] S. M. Morris Jr. Arginine Metabolism: Boundaries of Our Knowledge J. Nutr., June 1, 2007; 137(6): 1602S - 1609S. [Abstract] [Full Text] [PDF] P. J. Popovic, H. J. Zeh III, and J. B. Ochoa Arginine and Immunity J. Nutr., June 1, 2007; 137(6): 1681S - 1686S. [Abstract] [Full Text] [PDF] L. C. Jacobsen, K. Theilgaard-Monch, E. I. Christensen, and N. Borregaard Arginase 1 is expressed in myelocytes/metamyelocytes and localized in gelatinase granules of human neutrophils Blood, April 1, 2007; 109(7): 3084 - 3087. [Abstract] [Full Text] [PDF]

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