Dietary supplementation with L-arginine was shown to improve immune responses in various inflammatory models. However, the molecular mechanisms underlying L-arginine effects on immune cells remain unrecognized. Herein, we tested the hypothesis that a limitation of L-arginine could lead to the uncoupled state of murine macrophage inducible nitric oxide synthase and, therefore, increase inducible nitric-oxide-synthase-derived superoxide anion formation. Importantly, we demonstrated that L-arginine dose- and time dependently potentiated superoxide anion production in bacterial endotoxin-stimulated macrophages, although it did not influence NADPH oxidase expression and activity. Detailed analysis of macrophage activation showed the time dependence between LPS-induced iNOS expression and increased O(2)(∙-) formation. Moreover, downregulation of macrophage iNOS expression, as well as the inhibition of iNOS activity by NOS inhibitors, unveiled an important role of this enzyme in controlling O(2)(∙-) and peroxynitrite formation during macrophage stimulation. In conclusion, our data demonstrated that simultaneous induction of NADPH oxidase, together with the iNOS enzyme, can result in the uncoupled state of iNOS resulting in the production of functionally important levels of O(2)(∙-) soon after macrophage activation with LPS. Moreover, we demonstrated, for the first time that increased concentrations of L-arginine further potentiate iNOS-dependent O(2) (∙-) formation in inflammatory macrophages.

• MeSH
• aktivace enzymů MeSH
• arginin imunologie   MeSH
• biopteriny analogy a deriváty   metabolismus   MeSH
• buněčné linie MeSH
• časové faktory MeSH
• Escherichia coli imunologie   MeSH
• inhibitory enzymů farmakologie   MeSH
• lipopolysacharidy škodlivé účinky   MeSH
• makrofágy účinky léků   imunologie   metabolismus   MeSH
• myši MeSH
• NADPH-oxidasy metabolismus   MeSH
• NG-nitroargininmethylester farmakologie   MeSH
• oxid dusnatý metabolismus   MeSH
• respirační vzplanutí MeSH
• superoxidy metabolismus   MeSH
• synthasa oxidu dusnatého, typ II antagonisté a inhibitory   metabolismus   MeSH
• tyrosin analogy a deriváty   metabolismus   MeSH
• viabilita buněk MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH