Arginases in parasitic diseases

Vincendeau, Philippe; Gobert, Alain P.; Daulouède, Sylvie; Moynet, Daniel; Mossalayi, M. Djavad

doi:10.1016/s1471-4922(02)00010-7

Cited by 138 publications

(112 citation statements)

References 25 publications

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“…Arginase competes for the arginine substrate of iNOS by converting the amino acid to ornithine and liberating urea. Ornithine, in turn, is the immediate precursor for the synthesis of polyamines, essential growth factors for Leishmania (13). Thus, the balance between iNOS and arginase activities may determine whether the intracellular environment within the macrophage is microbicidal or supportive of Leishmania survival and multiplication.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, macrophages can be alternatively activated by other stimuli including IL-4 or IL-13 and express an arginase I activity that hydrolyzes arginine to urea and ornithine (8). Ornithine is a key intermediate in the synthesis of glutamine, proline, and polyamines in mammalian cells (13). However, in Leishmania promastigotes the sole role of ornithine is the production of polyamines, which are ubiquitous essential cations that play critical roles in a variety of cellular processes needed by proliferating cells (14,15).…”

mentioning

confidence: 99%

“…Specifically, IFN-␥ enhances expression of iNOS, whereas IL-4 induces both increased expression of the arginase protein and increased arginase activity (17). Furthermore, just as the type 1 and type 2 cytokines are mutually inhibitory, the induction of iNOS or arginase is also regulated in a reciprocal fashion (13). iNOS is regulated both at the level of activity and gene expression as well as by substrate (arginine) availability (17).…”

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confidence: 99%

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An Effect of Parasite-Encoded Arginase on the Outcome of Murine Cutaneous Leishmaniasis

Gaur¹,

Roberts

Dalvi³

et al. 2007

The Journal of Immunology

112

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Classical activation of macrophages infected with Leishmania species results in expression and activation of inducible NO synthase (iNOS) leading to intracellular parasite killing. Macrophages can contrastingly undergo alternative activation with increased arginase activity, metabolism of arginine along the polyamine pathway, and consequent parasite survival. An active role for parasite-encoded arginase in host microbicidal responses has not previously been documented. To test the hypothesis that parasite-encoded arginase can influence macrophage responses to intracellular Leishmania, a comparative genetic approach featuring arginase-deficient mutants of L. mexicana lacking both alleles of the gene encoding arginase (Δarg), as well as wild-type and complemented Δarg controls (Δarg[pArg]), was implemented. The studies showed: 1) the absence of parasite arginase resulted in a significantly attenuated infection of mice (p < 0.05); 2) poorer survival of Δarg in mouse macrophages than controls correlated with greater NO generation; 3) the difference between Δarg or control intracellular survival was abrogated in iNOS-deficient macrophages, suggesting iNOS activity was responsible for increased Δarg killing; 4) consistently, immunohistochemistry showed enhanced nitrotyrosine modifications in tissues of mice infected with Δarg compared with control parasites. Furthermore, 5) in the face of decreased parasite survival, lymph node cells draining cutaneous lesions of Δarg parasites produced more IFN-γ and less IL-4 and IL-10 than controls. These data intimate that parasite-encoded arginase of Leishmania mexicana subverts macrophage microbicidal activity by diverting arginine away from iNOS.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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An Effect of Parasite-Encoded Arginase on the Outcome of Murine Cutaneous Leishmaniasis

Gaur¹,

Roberts

Dalvi³

et al. 2007

The Journal of Immunology

112

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“…Arginase is an important player in the biochemistry of the immune system, especially with regard to function of the macrophage (Joerink et al, 2006). Extracellular arginase activity can deplete L-arginine as a macrophage strategy to deny a necessary substrate for proliferation and survival to malignant cells, virus-infected cells, fungi and parasites (Currie et al, 1979;Vincendeau et al, 2003). Intracellular arginase activity affords the enzyme an even bigger influence on functions of macrophages and other cell types such as endothelial cells and myocytes through its association with the pathway of the nitric oxide synthase (NOS) enzymes that produce nitric oxide (NO).…”

Section: Biological Effects In Fishmentioning

confidence: 99%

Criteria for Safe Use of Plant Ingredients in Diets for Aquacultured Fish

Hemre

Amlund

Aursand

et al. 2018

EJNFS

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“…Arginine is a common substrate for both arginase and nitric oxide (NO) synthase, the former leading to production of ornithine and the latter converting arginine to NO. The balance of NO/arginase activity is mutually regulated 14 and has been associated with 'classic' or 'alternative' MF activation. 15,16 Accordingly, we measured arginase activity and NO production in BMMF following activation with lipopolysaccharide (LPS) alone or LPS and interferon (IFN)-g in combination.…”

Section: Aplec Influences Clinical Outcome Of Hsv Infectionmentioning

confidence: 99%

The rat antigen-presenting lectin-like receptor complex influences innate immunity and development of infectious diseases

Guo

Verdrengh²,

Tarkowski³

et al. 2009

Genes Immun

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Genetic variation in the antigen-presenting lectin-like receptor gene complex (APLEC) associates with autoimmunity and arthritis in rats and humans. We hypothesized that the encoded C-type lectin-like receptors might influence innate immunity and responses to infectious agents. To test this hypothesis, we compared in vivo and in vitro phenotypes in DA rats and APLEC-congenic rats. Survival rates following infection with Staphylococcus aureus and Herpes simplex virus differed significantly between the two strains. Likewise, differential delayed type hypersensitivity (DTH), an immunological reaction involving T lymphocytes and macrophages, was observed in response to provocation with the chemical oxazolone. Unstimulated bone marrow-derived macrophages from the two strains appeared to already have polarized activation states with different mRNA levels of CD163 and Dectin-1 receptors. Following stimulation with a panel of microbial agents, differences in induced mRNA and protein levels were shown for interleukin (IL)-6 and IL-10 following stimulation with lipopolysaccharide, mannan and b-glucan. Expression levels of APLEC gene mRNAs also differed, and both strains had a notably dichotomous expression of the genes, with general downregulation of all four Dcir genes and upregulation of Mincle and Mcl. We suggest that human APLEC genes may similarly regulate infectious diseases, DTH and general macrophage activation status.

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Arginases in parasitic diseases

Cited by 138 publications

References 25 publications

An Effect of Parasite-Encoded Arginase on the Outcome of Murine Cutaneous Leishmaniasis

An Effect of Parasite-Encoded Arginase on the Outcome of Murine Cutaneous Leishmaniasis

Criteria for Safe Use of Plant Ingredients in Diets for Aquacultured Fish

The rat antigen-presenting lectin-like receptor complex influences innate immunity and development of infectious diseases

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