title: The unique role of dietary L-arginine in the acceleration of peritoneal macrophage sensitivity to bacterial endotoxin.
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 Ca(2+), 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.
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic vvi, Brno, Czech Republic. pekarovam@ibp.cz
authors.forename: Michaela
authors.initials: M
authors.lastname: Pekarova
authors.forename: Lukas
authors.initials: L
authors.lastname: Kubala
authors.forename: Hana
authors.initials: H
authors.lastname: Martiskova
authors.forename: Ivana
authors.initials: I
authors.lastname: Papezikova
authors.forename: Stanislava
authors.initials: S
authors.lastname: Kralova
authors.forename: Stephan
authors.initials: S
authors.lastname: Baldus
authors.forename: Anna
authors.initials: A
authors.lastname: Klinke
authors.forename: Radoslav
authors.initials: R
authors.lastname: Kuchta
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Kadlec
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Kuchtova
authors.forename: Hana
authors.initials: H
authors.lastname: Kolarova
authors.forename: Antonin
authors.initials: A
authors.lastname: Lojek
mesh_terms: D000818:Animals; D001120:Arginine / Q000276:immunology* / Q000494:pharmacology; D002460:Cell Line; D004032:Diet; D004731:Endotoxins / Q000276:immunology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D066298:In Vitro Techniques; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D010538:Peritonitis / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D004731:Endotoxins; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D048049:Extracellular Signal-Regulated MAP Kinases; D010738:Type C Phospholipases