Role of arginine metabolism in immunity and immunopathology

Peranzoni, Elisa; Marigo, Ilaria; Dolcetti, Luigi; Ugel, Stefano; Sonda, Nada; Taschin, Elisa; Mantelli, Barbara; Bronte, Vincenzo; Zanovello, Paola

doi:10.1016/j.imbio.2007.09.008

Cited by 143 publications

(133 citation statements)

References 174 publications

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“…The predominance of either enzyme spatially influences macrophage activation in different granuloma environments (8,(10)(11)(12)(13). In the presence of oxygen, NOS2 metabolizes L-arginine into L-citrulline and nitric oxide (NO), which is associated with killing of intracellular pathogens (10,(13)(14)(15). Arg1 hydrolyzes L-arginine, producing urea and L-ornithine, which can be further metabolized to downstream products such as polyamines; Arg1 activity is associated with anti-inflammatory responses (10,12,13,16).…”

mentioning

confidence: 99%

“…In the presence of oxygen, NOS2 metabolizes L-arginine into L-citrulline and nitric oxide (NO), which is associated with killing of intracellular pathogens (10,(13)(14)(15). Arg1 hydrolyzes L-arginine, producing urea and L-ornithine, which can be further metabolized to downstream products such as polyamines; Arg1 activity is associated with anti-inflammatory responses (10,12,13,16). Knowledge of the immune and inflammatory functions of NOS2 and Arg1 comes largely from murine studies (12,13).…”

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confidence: 99%

“…Arg1 hydrolyzes L-arginine, producing urea and L-ornithine, which can be further metabolized to downstream products such as polyamines; Arg1 activity is associated with anti-inflammatory responses (10,12,13,16). Knowledge of the immune and inflammatory functions of NOS2 and Arg1 comes largely from murine studies (12,13). Production of NO and other reactive nitrogen intermediates (RNIs) is a key protective mechanism against Mtb infection in mice because NOS2-deficient (Nos2 −/− ) mice infected with Mtb via aerosol and i.v.…”

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confidence: 99%

“…However, evidence from murine models of parasitic infection argues that Arg1 can have at least two other functions in addition to suppressing NOS2. First, macrophage Arg1 can reduce L-arginine availability to T cells, which are L-arginine auxotrophic, and can restrict local T-cell proliferation (10,13,(27)(28)(29). Arginine restriction is an essential Significance Tuberculosis (TB) granulomas represent sites of both bacterial containment and tissue pathology.…”

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confidence: 99%

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Macrophage arginase-1 controls bacterial growth and pathology in hypoxic tuberculosis granulomas

Duque-Correa¹,

Kühl

Rodríguez

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

114

109

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Lung granulomas develop upon Mycobacterium tuberculosis (Mtb) infection as a hallmark of human tuberculosis (TB). They are structured aggregates consisting mainly of Mtb-infected and -uninfected macrophages and Mtb-specific T cells. The production of NO by granuloma macrophages expressing nitric oxide synthase-2 (NOS2) via L-arginine and oxygen is a key protective mechanism against mycobacteria. Despite this protection, TB granulomas are often hypoxic, and bacterial killing via NOS2 in these conditions is likely suboptimal. Arginase-1 (Arg1) also metabolizes L-arginine but does not require oxygen as a substrate and has been shown to regulate NOS2 via substrate competition. However, in other infectious diseases in which granulomas occur, such as leishmaniasis and schistosomiasis, Arg1 plays additional roles such as T-cell regulation and tissue repair that are independent of NOS2 suppression. To address whether Arg1 could perform similar functions in hypoxic regions of TB granulomas, we used a TB murine granuloma model in which NOS2 is absent. Abrogation of Arg1 expression in macrophages in this setting resulted in exacerbated lung granuloma pathology and bacterial burden. Arg1 expression in hypoxic granuloma regions correlated with decreased T-cell proliferation, suggesting that Arg1 regulation of T-cell immunity is involved in disease control. Our data argue that Arg1 plays a central role in the control of TB when NOS2 is rendered ineffective by hypoxia.

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Macrophage arginase-1 controls bacterial growth and pathology in hypoxic tuberculosis granulomas

Duque-Correa¹,

Kühl

Rodríguez

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

114

109

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Randomized clinical trial of gut-specific nutrients in critically ill surgical patients

Gatt

MacFie

2010

British Journal of Surgery

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N‐Heterocyclic Tridentate Aromatic Ligands Bound to [Ln(hexafluoroacetylacetonate)₃] Units: Thermodynamic, Structural, and Luminescent Properties

Zaim

Nozary

Guénée

et al. 2012

Chemistry A European J

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Herein, we discuss how, why, and when cascade complexation reactions produce stable, mononuclear, luminescent ternary complexes, by considering the binding of hexafluoroacetylacetonate anions (hfac(-)) and neutral, semi-rigid, tridentate 2,6-bis(benzimidazol-2-yl)pyridine ligands (Lk) to trivalent lanthanide atoms (Ln(III)). The solid-state structures of [Ln(Lk)(hfac)(3)] (Ln=La, Eu, Lu) showed that [Ln(hfac)(3)] behaved as a neutral six-coordinate lanthanide carrier with remarkable properties: 1) the strong cohesion between the trivalent cation and the didentate hfac anions prevented salt dissociation; 2) the electron-withdrawing trifluoromethyl substituents limited charge-neutralization and favored cascade complexation with Lk; 3) nine-coordination was preserved for [Ln(Lk)(hfac)(3)] for the complete lanthanide series, whilst a counterintuitive trend showed that the complexes formed with the smaller lanthanide elements were destabilized. Thermodynamic and NMR spectroscopic studies in solution confirmed that these characteristics were retained for solvated molecules, but the operation of concerted anion/ligand transfers with the larger cations induced subtle structural variations. Combined with the strong red photoluminescence of [Eu(Lk)(hfac)(3)], the ternary system Ln(III)/hfac(-)/Lk is a promising candidate for the planned metal-loading of preformed multi-tridentate polymers.

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Role of arginine metabolism in immunity and immunopathology

Cited by 143 publications

References 174 publications

Macrophage arginase-1 controls bacterial growth and pathology in hypoxic tuberculosis granulomas

Macrophage arginase-1 controls bacterial growth and pathology in hypoxic tuberculosis granulomas

Randomized clinical trial of gut-specific nutrients in critically ill surgical patients

N‐Heterocyclic Tridentate Aromatic Ligands Bound to [Ln(hexafluoroacetylacetonate)₃] Units: Thermodynamic, Structural, and Luminescent Properties

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Role of arginine metabolism in immunity and immunopathology

Cited by 143 publications

References 174 publications

Macrophage arginase-1 controls bacterial growth and pathology in hypoxic tuberculosis granulomas

Macrophage arginase-1 controls bacterial growth and pathology in hypoxic tuberculosis granulomas

Randomized clinical trial of gut-specific nutrients in critically ill surgical patients

N‐Heterocyclic Tridentate Aromatic Ligands Bound to [Ln(hexafluoroacetylacetonate)3] Units: Thermodynamic, Structural, and Luminescent Properties

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N‐Heterocyclic Tridentate Aromatic Ligands Bound to [Ln(hexafluoroacetylacetonate)₃] Units: Thermodynamic, Structural, and Luminescent Properties