Metabolic fate of L-arginine in relation to microbiostatic capability of murine macrophages.

Granger, Donald L.; Hibbs, John B.; Perfect, John R.; Durack, David T.

doi:10.1172/jci114422

Cited by 337 publications

(211 citation statements)

References 39 publications

(37 reference statements)

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“…The apparent K m of NO synthesis by intact cells for extracellular arginine is approx. 73-150 µM [187,188], which is within the range of the K m values of the arginine transport systems (100-150 µM) [165] and of plasma arginine concentrations (Table 1). Immunohistochemical studies [189] demonstrated that CAT-1, eNOS and caveolin are co-localized in plasma-membrane caveolae, suggesting a preferential channelling or directed delivery of extracellular arginine to eNOS, as proposed previously [174].…”

Section: ) Complete Oxidation Of Arginine-derived 2-oxoglutarate Osupporting

confidence: 60%

“…Ornithine\urea production is the predominant route of arginine catabolism in unactivated rat endothelial cells [200,290], but NO production predominates when endothelial cells are stimulated with the appropriate combination of cytokines [200]. NO\citrulline synthesis represents the vast majority of arginine metabolism in rat macrophages [223], but ornithine\urea production dominates in murine macrophages [187,254,291]. These observations reflect the fact that arginase activity is greater in murine macrophages than in rat macrophages [201,292].…”

Section: Nosmentioning

confidence: 99%

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Arginine metabolism: nitric oxide and beyond

Morris

1998

Biochemical Journal

2,425

2,036

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Arginine is one of the most versatile amino acids in animal cells, serving as a precursor for the synthesis not only of proteins but also of nitric oxide, urea, polyamines, proline, glutamate, creatine and agmatine. Of the enzymes that catalyse rate-controlling steps in arginine synthesis and catabolism, argininosuccinate synthase, the two arginase isoenzymes, the three nitric oxide synthase isoenzymes and arginine decarboxylase have been recognized in recent years as key factors in regulating newly identified aspects of arginine metabolism. In particular, changes in the activities of argininosuccinate synthase, the arginases, the inducible isoenzyme of nitric oxide synthase and also cationic amino acid transporters play major roles in determining the metabolic fates of arginine in health and disease, and recent studies have identified

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Section: ) Complete Oxidation Of Arginine-derived 2-oxoglutarate Osupporting

confidence: 60%

Section: Nosmentioning

confidence: 99%

Arginine metabolism: nitric oxide and beyond

Morris

1998

Biochemical Journal

2,425

2,036

View full text Add to dashboard Cite

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“…In activated murine macrophages only 30% of cellular L-arginine metabolism occurs via NO synthase (Granger et al, 1990), though there is disagreement as to whether the flux of arginine to ornithine via arginase is concomitantly enhanced in activated macrophages (Benninghoff et al, 1991;Sato et al, 1992). We found increases in intracellular ornithine in J774 cells generating nitrite (Table 1) with negligible changes in extracellular ornithine (Table 2).…”

Section: Discussionmentioning

confidence: 76%

“…Expression of this enzyme is time-dependent, known to involve de novo protein synthesis and can be inhibited by glucocorticoids such as dexamethasone (Di Rosa et al, 1990;Assreuy & Moncada, 1992). The sustained production of NO is critically dependent on the presence of extracellular arginine (Drapier & Hibbs, 1988;Granger et al, 1990;Takema et al, 1991;Bogle et al, 1992a;Assreuy & Moncada, 1992).…”

Section: Introductionmentioning

confidence: 99%

Selective inhibition by dexamethasone of induction of NO synthase, but not of induction of l‐arginine transport, in activated murine macrophage J774 cells

Baydoun

Bogle

Pearson

et al. 1993

British J Pharmacology

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1 Effects of dexamethasone on induction of nitric oxide (NO) synathase and L-arginine transport by lipopolysaccharide (LPS) were examined in a murine cultured macrophage cell line J774. Metabolism of L-arginine to L-citrulline and subsequent changes in intracellular amino acids pools were correlated with changes in nitrite production. 3 Induction of NO synthase by LPS (1 jig ml-', 24 h) alone was accompanied by a marked increase in arginine utilisation leading to decreased intracellular arginine levels and elevated intracellular and extracellular L-citrulline levels. These changes were further enhanced in the presence of interferon-y (IFN-y, 100 units ml-', 24h).4 Dexamethasone (1 jaM) abolished the increases in both nitrite and citrulline production induced by LPS alone but only partially reversed the combined effects of LPS and IFN-y. In contrast, treatment of cells with dexamethasone (10 jtM) had no effect on the LPS-mediated induction of arginine transport or the decrease in intracellular arginine concentration. 5 We conclude that induction of arginine transporter activity in LPS-stimulated J774 cells involves de novo synthesis of carrier proteins, which increases transport of exogenous arginine during enhanced NO production. Moreover, the intracellular signalling pathways mediating induction of arginine transport and of NO synthase by LPS in activated macrophages diverge, since only the latter is sensitive to dexamethasone.

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“…pneumophila by a murine macrophage cell line, RAW 264.7 in vitro [28]. NO is generated via nitric oxide synthase, which uses L-arginine as sole substrate to produce citrulline and NO, which gives rise to nitrate and nitrite [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Differential nitric oxide (NO) production by macrophages from mice and guinea pigs infected with virulent and avirulent Legionella pneumophila serogroup 1

Rajagopalan-Levasseur

Lecointe

Bertrand

et al. 1996

Clinical and Experimental Immunology

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SUMMARYL-arginine-dependent reactive nitrogen intermediates have been identified as macrophage cytotoxic effector molecules against intracellular pathogens. To determine its role, ex vivo production of NO by peritoneal macrophages of C3H/HeN mice and Dunkin-Hartley guinea pigs infected intraperitoneally with a virulent and isogenic avirulent Legionella pneumophila serogroup 1 strain was compared with bacterial clearance from the lungs. While the virulent strain was cleared from mice lungs, the guinea pigs died within 96 h. In vivo infection with both strains resulted in the production of NO by mouse peritoneal macrophages ex vivo. In contrast, guinea pig macrophages did not produce detectable NO. In addition, infection by the avirulent strain led to the production of significantly more NO by mouse macrophages than the virulent parent strain, irrespective of stimulation with lipopolysaccharide (LPS) and/or interferon-gamma (IFN-°). These results suggest that resistance to Leg. pneumophila infection may depend on the production of NO by host macrophages.

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Metabolic fate of L-arginine in relation to microbiostatic capability of murine macrophages.

Abstract: L-arginine is required for the fungistatic action of murine macrophages in vitro. To

Cited by 337 publications

References 39 publications

Arginine metabolism: nitric oxide and beyond

Arginine metabolism: nitric oxide and beyond

Selective inhibition by dexamethasone of induction of NO synthase, but not of induction of l‐arginine transport, in activated murine macrophage J774 cells

Differential nitric oxide (NO) production by macrophages from mice and guinea pigs infected with virulent and avirulent Legionella pneumophila serogroup 1

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