L-arginine metabolites contribute to parasite elimination
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Nitric oxide (NO) is an important effector molecule of the immune system in eliminating numerous pathogens. Peritoneal macrophages fromTrypanosoma brucei brucei-infected mice express type II NO synthase (NOS-II), produce NO, and kill parasites in the presence ofl-arginine in vitro. Nevertheless, parasites proliferate in the vicinity of these macrophages in vivo. The present study shows thatl-arginine availability modulates NO production.
Trypanosomes use l-arginine for polyamine synthesis, required for DNA and trypanothione synthesis. Moreover, arginase activity is up-regulated in macrophages from infected mice from the first days of infection. Arginase competes with NOS-II for their common substrate, l-arginine. In vitro, arginase inhibitors decreased urea production, increased macrophage nitrite production, and restored trypanosome killing. In vivo, a dramatic decrease inl-arginine concentration was observed in plasma from infected mice.
In situ restoration of NO production and trypanosome killing were observed when excess l-arginine, but notd-arginine or l-arginine plusN ω-nitro-l-arginine (a NOS inhibitor), was injected into the peritoneum of infected mice. These data indicate the role of l-arginine depletion, induced by arginase and parasites, in modulating the l-arginine–NO pathway under pathophysiological conditions.
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Moreover, parasites use l-arginine in their polyamine metabolism. All these elements contribute to a decrease in plasma l-arginine in T. b. brucei-infected mice. This decrease in l-arginine, previously reported for Trypanosoma brucei gambiense-infected voles (30), may reduce NO production and alter parasite killing.
(NOS-II), produce NO, and kill parasites in the presence of L-arginine in vitro. … These data indicate the role of L-arginine depletion, induced by arginase and.
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different parasites escape nitric oxide (NO) toxicity is the activation of arginase. This leads to a depletion of L-arginine (substrate of NO synthase, resulting.
(PDF) L-Arginine Availability Modulates Local Nitric Oxide Production …
Jun 22, 2018 – Nevertheless, parasites proliferate in the vicinity of these macrophages in vivo. The present study shows thatl-arginine availability modulates …
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