Effects of<i>Mycobacterium bovis</i>BCG Infection on Regulation of<scp>l</scp>-Arginine Uptake and Synthesis of Reactive Nitrogen Intermediates in J774.1 Murine Macrophages

Peteroy-Kelly, Marcy A.; Venketaraman, Vishwanath; Connell, Nancy

doi:10.1128/iai.69.9.5823-5831.2001

Cited by 22 publications

(31 citation statements)

References 33 publications

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“…Treatment with IFN-␥ and LPS significantly decreased the expression of MCAT1 at 24 h compared to resting macrophages (P ϭ 0.0015). This result is consistent with our previous studies (40,41) and those of MacLeod et al (34), where downregulation of MCAT1 mRNA was observed in IFN-␥-plus-LPS-treated macrophages. BCG infection did not significantly change the levels of MCAT1 mRNA in J774.1 macrophages at either time point.…”

Section: Resultssupporting

confidence: 83%

“…As a control, infection of J774.1 cells with AS-2 (the AS-1 strain complemented with a copy of the wild-type Rv0522 gene) resulted in levels of arginine uptake similar to those of BCG-infected macrophages (P, 0.3255). Treatment with IFN-␥ plus LPS in the absence of infection resulted in a fivefold increase in arginine uptake over that of unstimulated macrophages (P, Ͻ0.0001), confirming earlier observations of our and other laboratories (7,31,40,41,46). Uptake by AS-1-infected cells showed similar levels of L-arginine uptake to J774.1 macrophages treated with IFN-␥ plus LPS (P, 0.1140).…”

Section: Resultssupporting

confidence: 79%

“…We showed that infection by BCG without activation does not stimulate arginine transport (40). We also found that AS-1, but not BCG, induced L-arginine uptake in infected J774.1 cells in the absence of activation with cytokines or lipopolysaccharide (LPS) (41).…”

supporting

confidence: 48%

“…J774.1 macrophages were exposed to the following experimental conditions: (i) stimulation with IFN-␥ plus LPS (100 U/ml and 1 g/ml, respectively); (ii) infection with BCG, AS- (40).…”

Section: Methodsmentioning

confidence: 99%

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Arginine Homeostasis in J774.1 Macrophages in the Context of Mycobacterium bovis BCG Infection

Talaue¹,

Venketaraman²,

Hazbón³

et al. 2006

J Bacteriol

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The competition for L-arginine between the inducible nitric oxide synthase and arginase contributes to the outcome of several parasitic and bacterial infections. The acquisition of L-arginine, however, is important not only for the host cells but also for the intracellular pathogen. In this study we observe that strain AS-1, the Mycobacterium bovis BCG strain lacking the Rv0522 gene, which encodes an arginine permease, perturbs L-arginine metabolism in J774.1 murine macrophages. Infection with AS-1, but not with wild-type BCG, induced L-arginine uptake in J774.1 cells. This increase in L-arginine uptake was independent of activation with gamma interferon plus lipopolysaccharide and correlated with increased expression of the MCAT1 and MCAT2 cationic amino acid transport genes. AS-1 infection also enhanced arginase activity in resting J774. Arginine is an essential modulator of the cellular immune response during infection. The generation of nitric oxide (NO) from arginine by the inducible nitric oxide synthase (iNOS) is responsible for the cytotoxicity of macrophages against bacterial and parasitic pathogens (10,25,37), while the conversion of arginine to ornithine and urea via the arginase pathway has been shown to support the intracellular survival of Helicobacter pylori, Leishmania spp., Trypanosoma spp., and Schistosoma spp. (1,9,20,21,28,33,44). Indeed, competition between iNOS and arginase for arginine has been suggested to contribute to the outcome of infection (11,35,36).Access to arginine is important not only for infected macrophages but also for the infecting organism. A number of pathogens have been shown to alter their arginine-dependent metabolic activities when they are inside their host cells. For example, Listeria monocytogenes preferentially upregulates arpJ, a gene encoding an arginine permease, during intracellular growth (32), Mycobacterium marinum induces the argS gene, encoding arginyl-tRNA synthetase, when inside macrophages (4), and Giardia lamblia inhibits NO synthesis by macrophages by directly consuming arginine using a highly efficient arginine transport system (15). Therefore, arginine availability and the capacity of the host cells and the infecting organism to acquire arginine and/or its derived substrates are important factors that can influence the course of an infection.The genes for L-arginine biosynthesis in Mycobacterium tuberculosis and Mycobacterium bovis BCG are found in the operon argCJBDFRGH (22). Although mycobacteria can synthesize L-arginine from glutamate, carbamoyl phosphate, and aspartate, L-arginine biosynthesis is energetically expensive as it requires at least six ATP equivalents; less energy is required for mycobacteria to acquire L-arginine from the external environment. Therefore, it is not surprising that there are several genes encoding putative L-arginine uptake systems (Rv0522, Rv2320c, Rv3253c, Rv1999c, and Rv1979c) in M. tuberculosis and M. bovis, most likely with different substrate affinities and capacities (13). Depending on the environment in which...

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Section: Resultssupporting

confidence: 83%

Section: Resultssupporting

confidence: 79%

supporting

confidence: 48%

“…J774.1 macrophages were exposed to the following experimental conditions: (i) stimulation with IFN-␥ plus LPS (100 U/ml and 1 g/ml, respectively); (ii) infection with BCG, AS- (40).…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Arginine Homeostasis in J774.1 Macrophages in the Context of Mycobacterium bovis BCG Infection

Talaue¹,

Venketaraman²,

Hazbón³

et al. 2006

J Bacteriol

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“…Nitric oxide assay-The generation of nitric oxide was assayed on stimulated mouse monocyte-macrophage cell line J774A.1 (ATCC, Manassas, VA; Peteroy- Kelly et al, 2001). The J774 cells cultured in pheno-red free DMEM (Cambrex, Walkersville, MD) plus 10% FBS (Hyclone, Logan, UT) were placed into the wells of a flat-bottom 96-well plate at 1.5×10 5 cells per well.…”

Section: Macrophage-stimulating Assaysmentioning

confidence: 99%

The immunomodulating neuropeptide alpha-melanocyte-stimulating hormone (α-MSH) suppresses LPS-stimulated TLR4 with IRAK-M in macrophages

Taylor

2005

Journal of Neuroimmunology

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Since α-MSH suppresses endotoxin-induced inflammation by innate immunity, it is possible that α-MSH can suppress the interface between innate and adaptive immunity mediated by TLR4-stimulated macrophages. Endotoxin-stimulated macrophages treated with α-MSH are suppressed in nitric oxide and IL-12p70 production, and cannot enhance antigen-stimulated IFN-γ production by Th1 cells. In macrophages treated with α-MSH, the inhibitory molecule IRAK-M is bound to IRAK-1, the proximal intracellular signal molecule of endotoxin-bound TLR4. These results further demonstrate the dynamic contribution of the nervous system, and the role of α-MSH in modulating the innate and adaptive immune interface in an inflammatory response.

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INFγ stimulates arginine transport through system y⁺L in human monocytes

et al. 2004

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Freshly isolated human monocytes transport L L -arginine mostly through a sodium independent, NEM insensitive pathway inhibited by L L -leucine in the presence, but not in the absence of sodium. Interferon-c (IFNc) stimulates this pathway, identifiable with system y þ L, and markedly enhances the expression of SLC7A7, the gene that encodes for system y þ L subunit y+LAT1, but not of SLC7A6, that codes for the alternative subunit y+LAT2. System y þ plays a minor role in arginine uptake by monocytes and the expression of system y þ -related genes, SLC7A1 and SLC7A2, is not changed by IFNc. These results demonstrate that system y þ L is sensitive to IFNc.

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Effects ofMycobacterium bovisBCG Infection on Regulation ofl-Arginine Uptake and Synthesis of Reactive Nitrogen Intermediates in J774.1 Murine Macrophages

Abstract: The generation of nitric oxide (NO) by activated macrophages is believed to control mycobacterial infection in the murine system. In this study we examined the effect of Mycobacterium bovis BCG infection on the L-arginine-dependent NO pathway in J774.1 murine macrophages. We

Cited by 22 publications

References 33 publications

Arginine Homeostasis in J774.1 Macrophages in the Context of Mycobacterium bovis BCG Infection

Arginine Homeostasis in J774.1 Macrophages in the Context of Mycobacterium bovis BCG Infection

The immunomodulating neuropeptide alpha-melanocyte-stimulating hormone (α-MSH) suppresses LPS-stimulated TLR4 with IRAK-M in macrophages

INFγ stimulates arginine transport through system y⁺L in human monocytes

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Effects ofMycobacterium bovisBCG Infection on Regulation ofl-Arginine Uptake and Synthesis of Reactive Nitrogen Intermediates in J774.1 Murine Macrophages

Abstract: The generation of nitric oxide (NO) by activated macrophages is believed to control mycobacterial infection in the murine system. In this study we examined the effect of Mycobacterium bovis BCG infection on the L-arginine-dependent NO pathway in J774.1 murine macrophages. We

Cited by 22 publications

References 33 publications

Arginine Homeostasis in J774.1 Macrophages in the Context of Mycobacterium bovis BCG Infection

Arginine Homeostasis in J774.1 Macrophages in the Context of Mycobacterium bovis BCG Infection

The immunomodulating neuropeptide alpha-melanocyte-stimulating hormone (α-MSH) suppresses LPS-stimulated TLR4 with IRAK-M in macrophages

INFγ stimulates arginine transport through system y+L in human monocytes

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INFγ stimulates arginine transport through system y⁺L in human monocytes