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• W1929563453 abstract "Microbicidal NO production is reliant on inducible NO synthase-mediated L-arginine metabolism in macrophages (MΦs). However, L-arginine supply can be restricted by arginase activity, resulting in inefficient NO output and inhibition of antimicrobial MΦ function. MΦs circumvent this by converting L-citrulline to L-arginine, thereby resupplying substrate for NO production. In this article, we define the metabolic signature of mycobacteria-infected murine MΦs supplied L-arginine, L-citrulline, or both amino acids. Using liquid chromatography-tandem mass spectrometry, we determined that L-arginine synthesized from L-citrulline was less effective as a substrate for arginase-mediated L-ornithine production compared with L-arginine directly imported from the extracellular milieu. Following Mycobacterium bovis bacillus Calmette-Guérin infection and costimulation with IFN-γ, we observed that MΦ arginase activity did not inhibit production of NO derived from L-citrulline, contrary to NO inhibition witnessed when MΦs were cultured in L-arginine. Furthermore, we found that arginase-expressing MΦs preferred L-citrulline over L-arginine for the promotion of antimycobacterial activity. We expect that defining the consequences of L-citrulline metabolism in MΦs will provide novel approaches for enhancing immunity, especially in the context of mycobacterial disease." @default.
• W1929563453 created "2016-06-24" @default.
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• W1929563453 date "2015-08-26" @default.
• W1929563453 modified "2023-10-12" @default.
• W1929563453 title "Differential Requirements for l-Citrulline and l-Arginine during Antimycobacterial Macrophage Activity" @default.
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• W1929563453 doi "https://doi.org/10.4049/jimmunol.1500800" @default.
• W1929563453 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6432794" @default.
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• W1929563453 hasPublicationYear "2015" @default.
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