Serum Arginase, a Biomarker of Treatment Efficacy in Human African Trypanosomiasis

Nzoumbou‐Boko, Romaric; Dethoua, Mariette; Gabriel, Frédéric; Buguet, Alain; Cespuglio, Raymond; Courtois, Pierrette; Daulouède, Sylvie; Bouteille, Bernard; Ngampo, Stéphane; Mpandzou, Ghislain Armel; Semballa, Silla; Vincendeau, Philippe

doi:10.1128/jcm.03371-12

Cited by 6 publications

(5 citation statements)

References 19 publications

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“…Meanwhile, there are some studies that have reported higher levels of arginase and polyamines (arginase products) in the sera and tissues of breast cancer patients [ 28 ]. Increased arginase activity probably causes damage to the host's immune response [ 29 ]. In our study, the arginase activity in the tissues of normal mice was significantly lower than in the therapeutic and control groups ( Figure 6B ).…”

Section: Discussionmentioning

confidence: 99%

Antitumor Effect of IP-10 by Using Two Different Approaches: Live Delivery System and Gene Therapy

et al. 2016

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PurposeImmunotherapy is one of the treatment strategies for breast cancer, the most common cancer in women worldwide. In this approach, the patient's immune system is stimulated to attack microscopic tumors and control metastasis. Here, we used interferon γ-induced protein 10 (IP-10), which induces and strengthens antitumor immunity, as an immunotherapeutic agent. We employed Leishmania tarentolae, a nonpathogenic lizard parasite that lacks the ability to persist in mammalian macrophages, was used as a live delivery system for carrying the immunotherapeutic agent. It has been already shown that arginase activity, and consequently, polyamine production, are associated with tumor progression.MethodsA live delivery system was constructed by stable transfection of pLEXSY plasmid containing the IP-10-enhanced green fluorescent protein (IP-10-egfp) fusion gene into L. tarentolae. Then, the presence of the IP-10-egfp gene and the accurate integration location into the parasite genome were confirmed. The therapeutic efficacy of IP-10 delivered via L. tarentolae and recombinant pcDNA-(IP-10-egfp) plasmid was compared by determining the arginase activity in a mouse 4T1 breast cancer model.ResultsThe pcDNA-(IP-10-egfp) group showed a significant reduction in tumor weight and growth. Histological evaluation also revealed that only this group demonstrated inhibition of metastasis to the lung tissue. The arginase activity in the tissue of the pcDNA-(IP-10-egfp) mice significantly decreased in comparison with that in normal mice. No significant difference was observed in arginase activity in the sera of mice receiving other therapeutic strategies.ConclusionOur data indicates that IP-10 immunotherapy is a promising strategy for breast cancer treatment, as shown in the 4T1-implanted BALB/c mouse model. However, the L. tarentolae-(IP-10-EGFP) live delivery system requires dose modifications to achieve efficacy in the applied regimen (six injections in 3 weeks). Our results indicate that the arginase assay could be a good biomarker to differentiate tumoral tissues from the normal ones.

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Section: Discussionmentioning

confidence: 99%

Antitumor Effect of IP-10 by Using Two Different Approaches: Live Delivery System and Gene Therapy

et al. 2016

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“…In human African trypanosomiasis caused by Trypanosoma gambiense, arginase serum levels increase and return to control values after treatment (9). Accordingly, in experimental murine infection by Trypanosoma brucei, host macrophage arginase activity represents a marker of susceptibility to the disease (10).…”

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confidence: 99%

Trypanosoma musculi Infection in Mice Critically Relies on Mannose Receptor–Mediated Arginase Induction by a TbKHC1 Kinesin H Chain Homolog

Nzoumbou‐Boko

Muylder

Semballa

et al. 2017

The Journal of Immunology

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Arginase activity induction in macrophages is an escape mechanism developed by parasites to cope with the host's immune defense and benefit from increased host-derived growth factor production. We report that arginase expression and activity were induced in macrophages during mouse infection by , a natural parasite of this host. This induction was reproduced in vitro by excreted/secreted factors of the parasite. A mAb directed toKHC1, an orphan kinesin H chain from , inhibited excreted/secreted factor-mediated arginase induction. Anti-KHC1 Ab also inhibited growth, both in vitro and in vivo. Induction of arginase activity and parasite growth involved C-type lectin receptors, because mannose injection decreased arginase activity induction and parasite load in vitro and in vivo. Accordingly, the parasite load was reduced in mice lacking mannose receptor C-type 1. The KHC1 homolog showed high similarity with KHC1. Bioinformatics analysis revealed the presence of homologs of this gene in other trypanosomes, including pathogens for humans and animals. Host metabolism dysregulation represents an effective parasite mechanism to hamper the host immune response and modify host molecule production to favor parasite invasion and growth. Thus, this orphan kinesin plays an important role in promoting trypanosome infection, and its neutralization or the lock of its partner host molecules offers promising approaches to increasing resistance to infection and new developments in vaccination against trypanosomiasis.

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“…Furthermore, arginase has been linked with various diseases, including those affecting the central nervous system, kidneys, the cardiovascular system, as well as immune dysfunction and cancer [ 1 ]. The essential role of arginase and inducible L-arginine metabolism in infectious diseases has been demonstrated in experimental trypanosomiasis and leishmaniasis and has since emerged as playing an important role in infections such as human African trypanosomiasis (HAT), AIDS, malaria, human leishmaniasis and COVID-19 [ 2 – 5 ]. Arginase induction is the hallmark of the type 2 immune response and alternative activation of macrophages and is also a marker of myeloid-derived suppressor cell activity.…”

Section: Introductionmentioning

confidence: 99%

“…The assessment of arginase activity with the Corraliza (modified Schimke’s method) micromethod is one of the most commonly used methods. This micromethod was initially employed to evaluate arginase activity in macrophages from infected mice and then in sera from HAT patients, as a biomarker of treatment efficacy [ 2 , 9 ]. The conventional Corraliza micromethod requires 50 µl of sample, several transfers between different types of tubes, and various pieces of relatively large equipment such as a water bath, an incubator, an oven, and spectrophotometer, making this procedure relatively labor-intensive.…”

Section: Introductionmentioning

confidence: 99%

Optimization of the arginase activity assay micromethod for macrophages and sera

Nzoumbou-Boko,

Zolipou,

Yambiyo

et al. 2023

BMC Res Notes

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Objective We optimized the spectrophotometric micromethod for the determination of arginase activity based on the Corraliza et al. modification of Schimke’s method. Arginase activity in sera from patients suffering from human African trypanosomiasis, in macrophage lysates from trypanosome-infected mice, and in purified bovine liver arginase was compared using the conventional and optimized micromethods. Results The sensitivity of both micromethods was comparable. However, our optimized method has the following advantages: it uses small sample volumes (6 µl per assay vs. 50 µl) and reagent volumes (200 µl vs. 400 µl), it can be carried out in a single microplate well, thereby minimizing handling, and it requires fewer materials and utilizes readily available equipment. Our optimized method proved to be applicable and well suited for small-volume samples and resource-poor laboratories.

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Serum Arginase, a Biomarker of Treatment Efficacy in Human African Trypanosomiasis

Cited by 6 publications

References 19 publications

Antitumor Effect of IP-10 by Using Two Different Approaches: Live Delivery System and Gene Therapy

Antitumor Effect of IP-10 by Using Two Different Approaches: Live Delivery System and Gene Therapy

Trypanosoma musculi Infection in Mice Critically Relies on Mannose Receptor–Mediated Arginase Induction by a TbKHC1 Kinesin H Chain Homolog

Optimization of the arginase activity assay micromethod for macrophages and sera

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