Accelerated senescence of human erythrocytes cultured with Plasmodium falciparum

Omodeo‐Salè, Fausta; Motti, Anna; Basilico, Nicoletta; Parapini, Silvia; Olliaro, Piero; Taramelli, Donatella

doi:10.1182/blood-2002-08-2437

Cited by 92 publications

(82 citation statements)

References 48 publications

(62 reference statements)

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“…When BODIPY 581/591-PC was used to probe P. falciparum-infected RBCs, we found an increase in the level of conversion of the chromophore to the oxidized form as the parasite matures. These data are consistent with previous studies indicating an overall increase in oxidative damage in infected RBCs (2,22,60), although these previous results could have been affected by inadvertent oxidation during sample work up (61). The increase in oxidative stress experienced by trophozoite-infected RBCs would be expected to increase their susceptibility to antimalarial drugs such as chloroquine that increase the levels of free FP-FeIII and are likely to exacerbate oxidative stress.…”

Section: Discussionsupporting

confidence: 82%

A phosphatidylcholine‐BODIPY 581/591 conjugate allows mapping of oxidative stress in P. falciparum‐infected erythrocytes

Klonis

Suarna

et al. 2009

Cytometry Pt A

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The chromophore, BODIPY 581/591, has an extended conjugated system that reacts with oxygen centered-radicals leading to changes in its spectral characteristics. Fatty acid-conjugated BODIPY 581/591 transfers readily between membrane bilayers and can be used as a sensor of oxidative stress in cell populations. We report here the use of a phosphatidylcholine (PC) derivative of BODIPY 581/591, which transfers much less rapidly between membranes. This allows the analysis of oxidative stress in individual cells and in different compartments within cells. Quantitative imaging and flow cytometry were used to measure the ratio of fully conjugated to oxidized probe in model systems and in Plasmodium falciparum-infected erythrocytes. We observed an increase in the oxidation of the parasite-associated BODIPY 581/591-PC as the intraerythrocytic parasite matures. By contrast, BODIPY 581/591-PC associated with the erythrocyte membrane experiences a low level of oxidation even in the later stages of parasite development. Treatment with a pro-oxidant compound caused increased oxidation of the probe in the parasite compartment, but less so in the host cell membrane. Conversely, treatment with ferricyanide increases oxidation of the probe in the erythrocyte cell membrane but does not inhibit parasite growth. Chromatographic analysis of the lipids in infected erythrocytes shows no evidence for loss of a-tocopherol or the accumulation of lipid hydroperoxides indicating that, despite the increased oxidative stress, the parasite membranes remain protected from substantial lipid oxidation. We have established BODIPY 581/591-PC as a useful probe of the spatial distribution of oxidative stress in P. falciparum-infected erythrocytes; however, the probe appears to be more sensitive to oxidative damage than endogenous lipids. ' 2009 International Society for Advancement of Cytometry Key terms malaria; Plasmodium falciparum; oxidative stress; BODIPY 581/591-PC; lipid oxidation OXIDATIVE damage to protein and membrane components plays important roles in various diseases and in the aging process (1), and a number of methods have been developed for measuring oxidative stress in cellular systems. In some studies, the levels of oxidized lipids and proteins have been measured directly (2,3). In other studies, secondary reaction products, such as malondialdehyde, have been used as a surrogate measure of lipid oxidation (4). These approaches offer useful insights into oxidative events; however, they usually require physical disruption of the system under investigation.Recently, fluorescence-based probes of oxidative stress have gained popularity as relatively nonperturbing sensors of cellular stresses (5-7). The fatty acid (FA) analogue, cis-paranaric acid (8), has been used as an oxidant-sensitive fluorophore; however, its fluorescence in the UV range is a disadvantage in some applications. BODIPY 581/591 is an alternative probe that can be excited in the visible range and

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Section: Discussionsupporting

confidence: 82%

A phosphatidylcholine‐BODIPY 581/591 conjugate allows mapping of oxidative stress in P. falciparum‐infected erythrocytes

Klonis

Suarna

et al. 2009

Cytometry Pt A

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“…Because circulating RBCs are anucleate and cannot synthesize new surface molecules, receptors that decay cannot be replaced; reticulocyte susceptibility to P. vivax may be related to higher Duffy-antigen density, for instance (20). If RBC susceptibility to P. malariae is related to senescence markers, the accelerated senescence of uninfected RBCs reported with P. falciparum (21) should greatly affect mixed-species infections (22). The common portrayal of P. falciparum as a generalist is complicated by evidence of a seeming preference for young RBCs (23), but more detailed resolution is needed here as well: our model shows that the proportion of RBCs that is in young age classes increases as an infection proceeds.…”

Section: Discussionmentioning

confidence: 99%

Age-structured red blood cell susceptibility and the dynamics of malaria infections

McQueen

McKenzie

2004

Proc. Natl. Acad. Sci. U.S.A.

100

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Malaria parasites and immune responses in an infected human interact on a dynamic landscape, in which a population of replicating parasites depletes a population of replenishing red blood cells (RBCs). These underlying dynamics receive relatively little attention, but they offer unique insights into the processes that control most malaria infections. Here, we focus on the observation that three of the four malaria-parasite species that infect humans are restricted to particular age classes of RBC. We explicitly incorporate this observation in models of infection dynamics to distinguish common from species-specific pressures on host immune responses, and we find that age structuring has profound effects on the course of infection. For all four species conditions exist under which the parasites may persist at low densities, or may clear, even in the absence of an immune response. Catastrophic anemia can occur even with the two species that attack only the youngest RBCs, although only a small fraction of cells are parasitized at any point. Furthermore, with these two, compensatory erythropoetic responses in the host accelerate parasite population growth. A ''basic reproduction rate'' characterizes these differences in outcomes.M alaria in a human begins with an inoculum of Plasmodium parasites from an Anopheles mosquito. The parasites penetrate liver cells, multiply, then enter the bloodstream, and invade red blood cells (RBCs), where they again multiply and burst the cells, each releasing 8-32 ''merozoites'' that invade more RBCs and continue the cycle. Almost all malaria pathology is associated with this blood stage replication cycle; it leads to geometric growth in the parasite population and to fevers, anemia, and sometimes death in the host (1).Parasite population growth is usually constrained by host immune responses. Accordingly, most mathematical models of within-host dynamics have taken the general form of predatorprey models, with the predator a population of immune agents and the prey a population of Plasmodium (2). A few Plasmodium falciparum models attempt to relate the dynamics of the parasite population to those of its prey, the population of RBCs, but none incorporate RBC aging or age-structured susceptibility (3-7).RBC age appears to be a strong constraint on malaria parasites, however: susceptibility to Plasmodium vivax or Plasmodium ovale invasion is said to be restricted to the very youngest circulating age class of RBCs, the ''reticulocytes,'' and Plasmodium malariae invasion to the very oldest (8, 9). P. falciparum, the species responsible for almost all the 1-3 million deaths attributed to malaria each year, seems promiscuous with respect to its RBC targets (10). It is widely assumed that these age constraints explain why counts of parasitized RBCs rarely exceed 25,000 per l with P. vivax, P. ovale, or P. malariae, but may reach 500,000 and beyond with P. falciparum, and thus, in turn, why fatal anemia occurs only in P. falciparum infections (11).Most malaria infections are not fatal, but the...

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“…During rapid growth and multiplying, plasmodium produces toxic redox active by-products that cause host haemoglobin degradation (20)(21)(22). Additionally, ROS are also produced by recruited and activated monocytes and neutrophils during infections that attack infected and uninfected erythrocytes, which increases the ROS level (22)(23)(24). Plasmodium cause damage in the membrane cells of infected and uninfected erythrocytes by inducing lipid peroxidation, leading to an aging-like process, eventually resulting in anemia (24).…”

Section: Discussionmentioning

confidence: 99%

Antiplasmodial properties of kaempferol-3-O-rhamnoside isolated from the leaves of Schima wallichii against chloroquine-resistant Plasmodium falciparum

et al. 2014

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Abstract. Previous intervention studies have shown that the most effective agents used in the treatment of malaria were isolated from natural sources. Plants consumed by non-human primates serve as potential drug sources for human disease management due to the similarities in anatomy, physiology and disease characteristics. The present study investigated the antiplasmodial properties of the primate-consumed plant, Schima wallichii (S. wallichii) Korth. (family Theaceae), which has already been reported to have several biological activities. The ethanol extract of S. wallichii was fractionated based on polarity using n-hexane, ethyl acetate and water. The antiplasmodial activity was tested in vitro against chloroquine-resistant Plasmodium falciparum (P. falciparum) at 100 µg/ml for 72 h. The major compound of the most active ethyl acetate fraction was subsequently isolated using column chromatography and identified by nuclear magnetic resonance. The characterized compound was also tested against chloroquine-resistant P. falciparum in culture to evaluate its antiplasmodial activity. The ethanol extract of S. wallichii at 100 µg/ml exhibited a significant parasite shrinkage after 24 h of treatment. The ethyl acetate fraction at 100 µg/ml was the most active fraction against chloroquine-resistant P. falciparum. Based on the structural characterization, the major compound isolated from the ethyl acetate fraction was kaempferol-3-O-rhamnoside, which showed promising antiplasmodial activity against chloroquine-resistant P. falciparum with an IC 50 of 106 µM after 24 h of treatment. The present study has provided a basis for the further investigation of kaempferol-3-O-rhamnoside as an active compound for potential antimalarial therapeutics.

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Accelerated senescence of human erythrocytes cultured with Plasmodium falciparum

Cited by 92 publications

References 48 publications

A phosphatidylcholine‐BODIPY 581/591 conjugate allows mapping of oxidative stress in P. falciparum‐infected erythrocytes

A phosphatidylcholine‐BODIPY 581/591 conjugate allows mapping of oxidative stress in P. falciparum‐infected erythrocytes

Age-structured red blood cell susceptibility and the dynamics of malaria infections

Antiplasmodial properties of kaempferol-3-O-rhamnoside isolated from the leaves of Schima wallichii against chloroquine-resistant Plasmodium falciparum

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