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The unique role of dietary l-arginine in the acceleration of peritoneal macrophage sensitivity to bacterial endotoxin

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Abstract

It is known that cells and organisms can indirectly “sense” changes in l-arginine availability via changes in the activity of various metabolic pathways. However, the mechanism(s) by which genes can be directly regulated by l-arginine in mammalian cells have not yet been elucidated. We investigated the effect of l-arginine in the in vivo model of peritoneal inflammation in mice and in vitro in RAW 264.7 macrophages. A detailed analysis of basic physiological functions and selected intracellular signaling cascades revealed that l-arginine is crucial for the acceleration of macrophage activation by bacterial lipopolysaccharide. l-arginine increased the production of reactive oxygen species, nitric oxide, release of Ca2+, as well as inducible nitric oxide synthase expression. Interestingly, the effect of l-arginine on macrophage activation was dependent on the phosphorylation of mitogen-activated protein kinases and activity of phospholipase C. In RAW 264.7 cells, l-arginine was shown to modulate the response of macrophages toward lipopolysaccharide via the activation of G-protein-coupled receptors. According to our data, we concluded that l-arginine availability plays a key role in the initiation of intracellular signaling pathways that trigger the lipopolysaccharide-induced inflammatory responses in murine macrophages. Although macrophages are partially stimulated in the absence of extracellular l-arginine, the presence of this amino acid significantly accelerates the sensitivity of macrophages to bacterial endotoxin.

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Acknowledgments

We thank Lenka Vystrcilova for excellent technical assistance, BioScience Writers and Jana Vaculikova for their expert grammar analysis. This work was supported by the Czech Science Foundation (524/08/1753), Masaryk University in Brno (MUNI/C/0886/2010), and by Academy of Science Czech Republic (M200041208).

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Authors and Affiliations

  1. Institute of Biophysics, Academy of Sciences of the Czech Republic v.v.i., Kralovopolska 135, 612 65, Brno, Czech Republic

    Michaela Pekarova, Lukas Kubala, Hana Martiskova, Ivana Papezikova, Stanislava Kralova, Hana Kolarova & Antonin Lojek

  2. International Clinical Research Center—Center of Biomolecular and Cellular Engineering, St. Anne’s University Hospital Brno, Brno, Czech Republic

    Lukas Kubala

  3. Department of Biochemistry, Faculty of Science, Masaryk University, Kotlarska 267/2, 611 37, Brno, Czech Republic

    Hana Martiskova

  4. Department of Cardiology, Hamburg University Heart Center, Martinistrasse 52, 20246, Hamburg, Germany

    Stephan Baldus & Anna Klinke

  5. Faculty of Electrical Engineering and Communication, Brno University of Technology, Technicka 3058/10, 616 00, Brno, Czech Republic

    Radoslav Kuchta, Jaroslav Kadlec & Zdenka Kuchtova

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  1. Michaela Pekarova
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Correspondence to Michaela Pekarova.

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Pekarova, M., Kubala, L., Martiskova, H. et al. The unique role of dietary l-arginine in the acceleration of peritoneal macrophage sensitivity to bacterial endotoxin. Immunol Res 56, 73–84 (2013). https://doi.org/10.1007/s12026-012-8379-2

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