Blood Changes and Enhanced Thromboxane and 6-Keto Prostaglandin F1α Production in Experimental Acute Plasmodium Bergei Infection in Hamsters

Essien, E M; Arnout, Jozef; Deckmyn, Hans; Vermylen, Jozef; Verstraete, Marc

doi:10.1055/s-0038-1661102

Cited by 10 publications

(5 citation statements)

References 7 publications

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“…This means that in our study it was the most significant compound among the studied oxylipins able to differentiate between malaria patients and controls. It was present at lower levels both in severe and uncomplicated patients, a fact that contradicts previous work conducted in a Plasmodium berghei hamster model [ 44 ]. TXB 2 is a non-enzymatic decomposition product of the unstable TXA 2 .…”

Section: Discussioncontrasting

confidence: 81%

The oxylipin and endocannabidome responses in acute phase Plasmodium falciparum malaria in children

Surowiec

Gouveia-Figueira

Orikiiriza

et al. 2017

Malar J

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BackgroundOxylipins and endocannabinoids are low molecular weight bioactive lipids that are crucial for initiation and resolution of inflammation during microbial infections. Metabolic complications in malaria are recognized contributors to severe and fatal malaria, but the impact of malaria infection on the production of small lipid derived signalling molecules is unknown. Knowledge of immunoregulatory patterns of these molecules in malaria is of great value for better understanding of the disease and improvement of treatment regimes, since the action of these classes of molecules is directly connected to the inflammatory response of the organism.MethodsDetection of oxylipins and endocannabinoids from plasma samples from forty children with uncomplicated and severe malaria as well as twenty controls was done after solid phase extraction followed by chromatography mass spectrometry analysis. The stable isotope dilution method was used for compound quantification. Data analysis was done with multivariate (principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA®) and univariate approaches (receiver operating characteristic (ROC) curves, t tests, correlation analysis).ResultsForty different oxylipin and thirteen endocannabinoid metabolites were detected in the studied samples, with one oxylipin (thromboxane B2, TXB2) in significantly lower levels and four endocannabinoids (OEA, PEA, DEA and EPEA) at significantly higher levels in infected individuals as compared to controls according to t test analysis with Bonferroni correction. Three oxylipins (13-HODE, 9-HODE and 13-oxo-ODE) were higher in severe compared to uncomplicated malaria cases according to the results from multivariate analysis. Observed changes in oxylipin levels can be connected to activation of cytochrome P450 (CYP) and 5-lipoxygenase (5-LOX) metabolic pathways in malaria infected individuals compared to controls, and related to increased levels of all linoleic acid oxylipins in severe patients compared to uncomplicated ones. The endocannabinoids were extremely responsive to malaria infection with majority of this class of molecules found at higher levels in infected individuals compared to controls.ConclusionsIt was possible to detect oxylipin and endocannabinoid molecules that can be potential biomarkers for differentiation between malaria infected individuals and controls and between different classes of malaria. Metabolic pathways that could be targeted towards an adjunctive therapy in the treatment of malaria were also pinpointed.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-017-2001-y) contains supplementary material, which is available to authorized users.

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Section: Discussioncontrasting

confidence: 81%

The oxylipin and endocannabidome responses in acute phase Plasmodium falciparum malaria in children

Surowiec

Gouveia-Figueira

Orikiiriza

et al. 2017

Malar J

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“…The phenomenon was first observed in rodent infection experiments in the 1950s and has been regularly (and frequently) reported over the decades since. Thrombocytopenia is consistently seen in animal models of the disease, including in hamsters infected with Plasmodium berghei , a rodent malaria , in P. vinckei ‐infected mice and P. chabaudi ‐infected mice , and is particularly severe in P. knowlesi ‐infected macaque monkeys .…”

Section: Thrombocytopenia In Malaria – Occurrence Clinical Corollarimentioning

confidence: 99%

Immune role of platelets in malaria

McMorran

2018

ISBT Science Series

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Plasmodium infections causing malaria threaten over 3 billion people from more than ninety countries. Despite control efforts spanning several decades, there are still more than 400,000 fatalities annually. Survival to malaria is largely determined by the host response mounted against the parasite, and the ensuing balance of inflammatory, tissue‐damaging reactions and immune‐mediated mechanisms directed towards controlling pathogen growth. Platelets appear to play important roles in each of these processes. On one hand, platelets have been implicated adversely in cerebral malaria, a severe disease manifestation where microvascular occlusions develop in the brain, leading to inflammatory foci and brain swelling, and causing coma and often death. Platelets adhere to the cerebral endothelium and mediate accumulation of infected erythrocytes in the brain, with the postulated outcome of increasing severity or of even mediating this disease. On the other hand, platelets can directly kill parasites in the periphery by binding to infected red cells and thereby contribute to the host's ability to control the infection. Platelet binding to infected red cells releases an antimicrobial protein, platelet factor 4 (PF4), which accumulates inside the cell and kills the parasite by lysing the food vacuole. The Duffy antigen, a red cell‐expressed receptor of PF4, is required for the PF4 accumulation and parasite killing. Further understanding of the roles of platelets in malaria, especially in clinical disease, is required. This knowledge may provide novel interventions and therapeutic tools, which are so desperately needed.

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“…Increased thromboxane levels have been found in hamsters [40], P-selectin levels were increased in infected mice [41,42] and platelet caspase activation was seen in infected mice [43], as well as increased levels of platelet microparticles [43], all of which are markers of platelet activation. Using MRI in a mouse model of cerebral malaria, adhesion of activated platelets to the cerebrovascular endothelium was detected [44].…”

Section: Platelet Activationmentioning

confidence: 99%

The role of platelets in the pathogenesis of cerebral malaria

Cox

McConkey

2009

Cell. Mol. Life Sci.

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Malaria is a major cause of morbidity and mortality in the developing world and cerebral malaria is responsible for the majority of malaria-associated deaths. There is a strong association between thrombocytopenia and outcome in malaria, suggesting a role for platelets in the pathogenesis of malaria. This thrombocytopenia is likely due to platelet activation possibly through an interaction between PfEMP1 on plasmodium and CD36 on platelets. Platelet activation by plasmodium has two potential consequences. It can lead to the formation of micro-aggregates of infected red blood cells and platelets which can occlude blood vessels and it also leads to binding to and activation of the endothelium.

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Blood Changes and Enhanced Thromboxane and 6-Keto Prostaglandin F1α Production in Experimental Acute Plasmodium Bergei Infection in Hamsters

Cited by 10 publications

References 7 publications

The oxylipin and endocannabidome responses in acute phase Plasmodium falciparum malaria in children

The oxylipin and endocannabidome responses in acute phase Plasmodium falciparum malaria in children

Immune role of platelets in malaria

The role of platelets in the pathogenesis of cerebral malaria

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