Reduced erythrocyte deformability associated with hypoargininemia during Plasmodiumfalciparum malaria

Rey, Juliana; Buffet, Pierre; Ciceron, Liliane; Milon, Geneviève; Mercereau‐Puijalon, Odile; Safeukui, Innocent

doi:10.1038/srep03767

Cited by 18 publications

(11 citation statements)

References 56 publications

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“…Disruption of erythrocyte NO metabolism by the parasite could contribute to the reduced deformability of the erythrocyte and thereby could inhibit circulation of infected erythrocytes through capillaries. Rey and colleagues recently demonstrated that the deformability of infected erythrocytes is, in part, dependent on exogenous arginine, and hence NO biosynthesis (Rey et al, 2014). The molecular identity of the enzyme(s) involved is yet to be resolved, as is that of the high-affinity transporter, which mediates the uptake of arginine into the parasite, thereby depleting arginine from the host cell compartment.…”

Section: Discussionmentioning

confidence: 99%

“…More recently, it was reported that there is, in the parasite, a pool of NO localized to the digestive vacuole (Ostera et al, 2008); however, no citrulline production was detected, and it was proposed that the parasite's NO pool is maintained not by a NOS but by the ingestion of host cell cytosol and the subsequent conversion of host nitrate to NO by an unknown parasite nitrate reductase (Ostera et al, 2008;Ostera et al, 2011). By contrast, Rey and colleagues reported that there to be an NO pool present throughout the parasite, sustained by an arginine-dependent pathway (Rey et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Sequestration and metabolism of host cell arginine by the intraerythrocytic malaria parasitePlasmodium falciparum

Cobbold

Llinás

Kirk

2016

Cellular Microbiology

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Human erythrocytes have an active nitric oxide synthase, which converts arginine into citrulline and nitric oxide (NO). NO serves several important functions, including the maintenance of normal erythrocyte deformability, thereby ensuring efficient passage of the red blood cell through narrow microcapillaries. Here, we show that following invasion by the malaria parasite Plasmodium falciparum the arginine pool in the host erythrocyte compartment is sequestered and metabolized by the parasite. Arginine from the extracellular medium enters the infected cell via endogenous host cell transporters and is taken up by the intracellular parasite by a high-affinity cationic amino acid transporter at the parasite surface. Within the parasite arginine is metabolized into citrulline and ornithine. The uptake and metabolism of arginine by the parasite deprive the erythrocyte of the substrate required for NO production and may contribute to the decreased deformability of infected erythrocytes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sequestration and metabolism of host cell arginine by the intraerythrocytic malaria parasitePlasmodium falciparum

Cobbold

Llinás

Kirk

2016

Cellular Microbiology

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“…Plasmodium falciparum produces an arginase resulting in hypoargininemia, decreasing the bioavailability of nitrogen atoms for nitric oxide synthesis by erythrocytes. This decreases the deformability of both parasitized and unparasitized erythrocytes [32]. Malarial infection also causes extensive remodeling of the erythrocyte cell membrane, which decreases its zeta potential, fostering erythrocyte aggregation [33].…”

Section: Review the Association Of Infection With Myocardial Infarctionmentioning

confidence: 99%

The Role of Blood Viscosity in Infectious Diseases

Sloop¹,

Mast²,

Pop³

et al. 2020

Cureus

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Blood viscosity is increased by elevated concentrations of acute phase reactants and hypergammaglobulinemia in inflammation. These increase blood viscosity by increasing plasma viscosity and fostering erythrocyte aggregation. Blood viscosity is also increased by decreased erythrocyte deformability, as occurs in malaria. Increased blood viscosity contributes to the association of acute infections with myocardial infarction (MI), venous thrombosis, and venous thromboembolism. It also increases vascular resistance, which decreases tissue perfusion and activates stretch receptors in the left ventricle, thereby initiating the systemic vascular resistance response. This compensates for the increased vascular resistance by vasodilation, lowering hematocrit, and decreasing intravascular volume. This physiological response causes the anemias associated with malaria, chronic inflammation, and other chronic diseases. Since tissue perfusion is inversely proportional to blood viscosity, anemia may be beneficial as it increases tissue perfusion when erythrocyte aggregating factors or erythrocytes with decreased deformability are present in the blood.

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“…It was reported that P. falciparum parasites under the pressure of S-nitroso-N-acetyl-penicillamine (SNAP), the NO donor, died by autophagic-like cell death (Totino et al 2008). Another study showed that NO production increased in P. falciparum parasites incubated with L-Arg in vitro (Rey et al 2014). These results suggest that L-Arg supplementation may have a direct effect on the viability of malaria parasites in vivo, and more work needs to be done to prove it.…”

Section: Discussionmentioning

confidence: 99%

L-Arginine Exacerbates Experimental Cerebral Malaria by Enhancing Pro-Inflammatory Responses

Feng

Chen³

et al. 2015

Tohoku J. Exp. Med.

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L-Arginine (L-Arg), the substrate for nitric oxide (NO) synthase, has been used to treat malaria to reverse endothelial dysfunction in adults. However, the safety and efficacy of L-Arg remains unknown in malaria patients under the age of five, who are at the greatest risk of developing cerebral malaria (CM), a severe malaria complication. Here, we tested effects of L-Arg treatment on the outcomes of CM using a mouse model. Experimental cerebral malaria (ECM) was induced in female C57BL/6 mice infected with Plasmodium berghei ANKA, and L-Arg was administrated either prophylactically or after parasite infection. ) in the spleen. The levels of pro-inflammatory cytokines, IFN-γ and TNF-α, in splenocyte cultures were also increased by L-Arg treatment. The above changes were accompanied with a rise in the number of dendritic cells (DCs) and an increase in their maturation. However, L-Arg did not affect the population of regulatory T cells or the level of IL-10 in the spleen. Taken together, these data suggest that L-Arg may enhance the Th1 immune response, which is essential for a protective response in uncomplicated malaria but could be lethal in CM patients. Therefore, the prophylactic use of L-Arg to treat CM, based on the assumption that restoring the bioavailability of endothelial NO improves the outcome of CM, may need to be reconsidered especially for children.

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Reduced erythrocyte deformability associated with hypoargininemia during Plasmodiumfalciparum malaria

Cited by 18 publications

References 56 publications

Sequestration and metabolism of host cell arginine by the intraerythrocytic malaria parasitePlasmodium falciparum

Sequestration and metabolism of host cell arginine by the intraerythrocytic malaria parasitePlasmodium falciparum

The Role of Blood Viscosity in Infectious Diseases

L-Arginine Exacerbates Experimental Cerebral Malaria by Enhancing Pro-Inflammatory Responses

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