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*
Max-Planck-Institut für Immunbiologie, Freiburg, Germany; and
Departamento de Bioquímica y Biología Molecular, Facultad de Veterinaria, Universidad de Extremadura, Cáceres, Spain
Activated murine macrophages metabolize arginine by two alternative
pathways involving the enzymes inducible NO synthase (iNOS) or
arginase. The balance between the two enzymes is competitively
regulated by Th1 and Th2 T helper cells via their secreted cytokines:
Th1 cells induce iNOS, whereas Th2 cells induce arginase. Whereas the
role of macrophages expressing iNOS as inflammatory cells is well
established, the functional competence of macrophages expressing
arginase remains a matter of speculation. Two isoforms of mammalian
arginases exist, hepatic arginase I and extrahepatic arginase II. We
investigated the regulation of arginase isoforms in murine bone
marrow-derived macrophages (BMM
) in the context of Th1 and Th2
stimulation. Surprisingly, in the presence of either Th2 cytokines or
Th2 cells, we observe a specific induction of the hepatic isoform
arginase I in BMM. Induction of arginase I was shown on the mRNA and
protein levels and obeyed the recently demonstrated synergism among the
Th2 cytokines IL-4 and IL-10. Arginase II was detectable in
unstimulated BMM and was not significantly modulated by Th1 or Th2
stimulation. Similar to murine BMM, murine bone marrow-derived
dendritic cells, as well as a dendritic cell line, up-regulated
arginase I expression and arginase activity upon Th2 stimulation,
whereas arginase II was never detected. In addition to revealing the
unexpected expression of arginase I in the macrophage/monocyte lineage,
these results uncover a further intriguing parallelism between iNOS and
arginase: both have a constitutive and an inducible isoform, the latter
regulated by the Th1/Th2 balance.
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R. Lang, D. Patel, J. J. Morris, R. L. Rutschman, and P. J. Murray Shaping Gene Expression in Activated and Resting Primary Macrophages by IL-10 J. Immunol., September 1, 2002; 169(5): 2253 - 2263. [Abstract] [Full Text] [PDF]
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 J. Huang, F. J. DeGraves, S. D. Lenz, D. Gao, P. Feng, D. Li, T. Schlapp, and B. Kaltenboeck The quantity of nitric oxide released by macrophages regulates Chlamydia-induced disease PNAS, March 19, 2002; 99(6): 3914 - 3919. [Abstract] [Full Text] [PDF]
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A. C. Morrison and P. H. Correll Activation of the Stem Cell-Derived Tyrosine Kinase/RON Receptor Tyrosine Kinase by Macrophage-Stimulating Protein Results in the Induction of Arginase Activity in Murine Peritoneal Macrophages J. Immunol., January 15, 2002; 168(2): 853 - 860. [Abstract] [Full Text] [PDF]
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E. A. Patton, A. C. La Flamme, J. A. Pedras-Vasoncelos, and E. J. Pearce Central Role for Interleukin-4 in Regulating Nitric Oxide-Mediated Inhibition of T-Cell Proliferation and Gamma Interferon Production in Schistosomiasis Infect. Immun., January 1, 2002; 70(1): 177 - 184. [Abstract] [Full Text] [PDF]
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T. Ravasi, C. Wells, A. Forest, D. M. Underhill, B. J. Wainwright, A. Aderem, S. Grimmond, and D. A. Hume Generation of Diversity in the Innate Immune System: Macrophage Heterogeneity Arises from Gene-Autonomous Transcriptional Probability of Individual Inducible Genes J. Immunol., January 1, 2002; 168(1): 44 - 50. [Abstract] [Full Text] [PDF]
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M. Hesse, M. Modolell, A. C. La Flamme, M. Schito, J. M. Fuentes, A. W. Cheever, E. J. Pearce, and T. A. Wynn Differential Regulation of Nitric Oxide Synthase-2 and Arginase-1 by Type 1/Type 2 Cytokines In Vivo: Granulomatous Pathology Is Shaped by the Pattern of L-Arginine Metabolism J. Immunol., December 1, 2001; 167(11): 6533 - 6544. [Abstract] [Full Text] [PDF]
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P. Dickie, A. Roberts, and R. Lee A defect in HIV-1 transgenic murine macrophages results in deficient nitric oxide production J. Leukoc. Biol., October 1, 2001; 70(4): 592 - 600. [Abstract] [Full Text] [PDF]
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L. C. Gavrilescu and E. Y. Denkers IFN-{{gamma}} Overproduction and High Level Apoptosis Are Associated with High but Not Low Virulence Toxoplasma gondii Infection J. Immunol., July 15, 2001; 167(2): 902 - 909. [Abstract] [Full Text] [PDF]
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B. Namangala, P. De Baetselier, W. Noël, L. Brys, and A. Beschin Alternative versus classical macrophage activation during experimental African trypanosomosis J. Leukoc. Biol., March 1, 2001; 69(3): 387 - 396. [Abstract] [Full Text]
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R. Rutschman, R. Lang, M. Hesse, J. N. Ihle, T. A. Wynn, and P. J. Murray Cutting Edge: Stat6-Dependent Substrate Depletion Regulates Nitric Oxide Production J. Immunol., February 15, 2001; 166(4): 2173 - 2177. [Abstract] [Full Text] [PDF]
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A. P. Gobert, S. Daulouede, M. Lepoivre, J. L. Boucher, B. Bouteille, A. Buguet, R. Cespuglio, B. Veyret, and P. Vincendeau L-Arginine Availability Modulates Local Nitric Oxide Production and Parasite Killing in Experimental Trypanosomiasis Infect. Immun., August 1, 2000; 68(8): 4653 - 4657. [Abstract] [Full Text] [PDF]
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C. D. Mills, K. Kincaid, J. M. Alt, M. J. Heilman, and A. M. Hill M-1/M-2 Macrophages and the Th1/Th2 Paradigm J. Immunol., June 15, 2000; 164(12): 6166 - 6173. [Abstract] [Full Text] [PDF]
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