L-Arginine and tetrahydrobiopterin supported nitric oxide production is crucial for the microbicidal activity of neutrophils

Nagarkoti, Sheela; Sadaf, Samreen; Awasthi, Deepika; Chandra, Tulika; Jagavelu, Kumaravelu; Kumar, Sachin; Dikshit, Madhu

doi:10.1080/10715762.2019.1566605

Cited by 17 publications

(15 citation statements)

References 65 publications

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“…On the other hand, arginine can also enhance the phagocytosis of Staphylococcus aureus by human neutrophils [162] and sustain the synthesis of NO by mouse neutrophils [163]. NO synthesis in neutrophils can also exert a protective role, in this case, by preventing the production of highly damaging superoxide by these cells [164,165].…”

Section: Granulocytes: Neutrophilsmentioning

confidence: 99%

Arginine-dependent immune responses

Líndez

Reith

2021

Cell. Mol. Life Sci.

112

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A growing body of evidence indicates that, over the course of evolution of the immune system, arginine has been selected as a node for the regulation of immune responses. An appropriate supply of arginine has long been associated with the improvement of immune responses. In addition to being a building block for protein synthesis, arginine serves as a substrate for distinct metabolic pathways that profoundly affect immune cell biology; especially macrophage, dendritic cell and T cell immunobiology. Arginine availability, synthesis, and catabolism are highly interrelated aspects of immune responses and their fine-tuning can dictate divergent pro-inflammatory or anti-inflammatory immune outcomes. Here, we review the organismal pathways of arginine metabolism in humans and rodents, as essential modulators of the availability of this semi-essential amino acid for immune cells. We subsequently review well-established and novel findings on the functional impact of arginine biosynthetic and catabolic pathways on the main immune cell lineages. Finally, as arginine has emerged as a molecule impacting on a plethora of immune functions, we integrate key notions on how the disruption or perversion of arginine metabolism is implicated in pathologies ranging from infectious diseases to autoimmunity and cancer.

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Section: Granulocytes: Neutrophilsmentioning

confidence: 99%

Arginine-dependent immune responses

Líndez

Reith

2021

Cell. Mol. Life Sci.

112

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“…In normal conditions, NOS catalyzes the transformation of arginine, O 2 , and NADPH-derived electrons to NO and citrulline ( Figure 1 ). However, in the presence of pathologic conditions like atherosclerosis and diabetes, the NOS function is altered, and the enzyme catalyzes the reduction of O 2 to superoxide (O 2 − ), a phenomenon that is generally referred to as “NOS uncoupling” [ 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ], and has been linked to a limited bioavailability of tetrahydrobiopterin (BH4, also known as sapropterin) [ 42 , 43 , 44 , 45 , 46 , 47 ]. Indeed, the donation of an electron by BH4 to produce a transient BH4 •+ radical is required for the oxidation of arginine to citrulline and the associated formation of a ferrous iron–NO complex at the NOS heme catalytic center [ 48 , 49 , 50 , 51 ].…”

Section: Pleiotropic Effects Of Argininementioning

confidence: 99%

Arginine and Endothelial Function

et al. 2020

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Arginine (L-arginine), is an amino acid involved in a number of biological processes, including the biosynthesis of proteins, host immune response, urea cycle, and nitric oxide production. In this systematic review, we focus on the functional role of arginine in the regulation of endothelial function and vascular tone. Both clinical and preclinical studies are examined, analyzing the effects of arginine supplementation in hypertension, ischemic heart disease, aging, peripheral artery disease, and diabetes mellitus.

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“…The availability of arginine, a common substrate to ARG1 and NOS2, can regulate the levels of CAT1 and CAT2 transporters in the external plasmatic membrane and the parasitophorous vacuole [19,46,47]. This complex regulation in arginine uptake is one of the multiple factors involved in regulating production during Leishmania infection through Nos2 transcription and NOS2 translation and through the presence of the substrates and co-factors such as O2, biopterin, NADPH, and others [48]. As previously shown, the B6-macrophages only increased Nos2, NOS2, and NO production when miRNA let-7e was inhibited during L. amazonensis infection, reducing the infectivity [28].…”

Section: Discussionmentioning

confidence: 99%

miR-294 and miR-410 Negatively Regulate Tnfa, Arginine Transporter Cat1/2, and Nos2 mRNAs in Murine Macrophages Infected with Leishmania amazonensis

Acuña

Zanatta

Bento

et al. 2022

ncRNA

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MicroRNAs are small non-coding RNAs that regulate cellular processes by the post-transcriptional regulation of gene expression, including immune responses. The shift in the miRNA profiling of murine macrophages infected with Leishmania amazonensis can change inflammatory response and metabolism. L-arginine availability and its conversion into nitric oxide by nitric oxide synthase 2 (Nos2) or ornithine (a polyamine precursor) by arginase 1/2 regulate macrophage microbicidal activity. This work aimed to evaluate the function of miR-294, miR-301b, and miR-410 during early C57BL/6 bone marrow-derived macrophage infection with L. amazonensis. We observed an upregulation of miR-294 and miR-410 at 4 h of infection, but the levels of miR-301b were not modified. This profile was not observed in LPS-stimulated macrophages. We also observed decreased levels of those miRNAs target genes during infection, such as Cationic amino acid transporters 1 (Cat1/Slc7a1), Cat2/Slc7a22 and Nos2; genes were upregulated in LPS stimuli. The functional inhibition of miR-294 led to the upregulation of Cat2 and Tnfa and the dysregulation of Nos2, while miR-410 increased Cat1 levels. miR-294 inhibition reduced the number of amastigotes per infected macrophage, showing a reduction in the parasite growth inside the macrophage. These data identified miR-294 and miR-410 biomarkers for a potential regulator in the inflammatory profiles of microphages mediated by L. amazonensis infection. This research provides novel insights into immune dysfunction contributing to infection outcomes and suggests the use of the antagomiRs/inhibitors of miR-294 and miR-410 as new therapeutic strategies to modulate inflammation and to decrease parasitism.

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L-Arginine and tetrahydrobiopterin supported nitric oxide production is crucial for the microbicidal activity of neutrophils

Cited by 17 publications

References 65 publications

Arginine-dependent immune responses

Arginine-dependent immune responses

Arginine and Endothelial Function

miR-294 and miR-410 Negatively Regulate Tnfa, Arginine Transporter Cat1/2, and Nos2 mRNAs in Murine Macrophages Infected with Leishmania amazonensis

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