An Analysis of the Binding Characteristics of a Panel of Recently Selected ICAM-1 Binding Plasmodium falciparum Patient Isolates

Madkhali, Aymen M; Alkurbi, Mohammed O; Szestak, Tadge; Bengtsson, Anja; Patil, Pradeep R.; Wu, Yang; Al-Harthi, Saeed A.; Jensen, Anja T. R.; Pleass, Richard J.; Craig, Alister G.

doi:10.1371/journal.pone.0111518

Cited by 21 publications

(35 citation statements)

References 54 publications

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“…More than 90% of the UM and 75% of the CM cases were used in the 1 st or 2 nd cycle. The binding assay under flow conditions was performed using the Cellix microfluidics system (https://cel lixltd.com/), as previously described (Madkhali et al, 2014). Briefly, HBMEC (Cell Systems, US) or HDMEC (Promocell, Germany) were cultured as per manufacturer's instructions and used up to passage 9, whilst retaining their endothelial characteristics as shown in Appendix Fig S1. The cells were stimulated overnight with 10 ng/ml TNF, dislodged with Accutase â and seeded in Vena8 biochips (Cellix) coated with 100 lg/ml fibronectin.…”

Section: Binding To Microvascular Endothelial Cells Under Flowmentioning

confidence: 99%

“…A number of studies have investigated cytoadherence of specific PfEMP1 variants to human microvascular endothelial cells, but these have been with laboratory strains or PfEMP1-modified parasites (Madkhali et al, 2014;Gillrie et al, 2015). Patient isolates have also been investigated for their binding phenotype, but mainly on purified protein and mostly under static conditions (Craig et al, 2012;Almelli et al, 2014;Mahamar et al, 2017;Ndam et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

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Cerebral malaria is associated with differential cytoadherence to brain endothelial cells

et al. 2019

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Sequestration of Plasmodium falciparum‐infected erythrocytes (IE) within the brain microvasculature is a hallmark of cerebral malaria (CM). Using a microchannel flow adhesion assay with TNF‐activated primary human microvascular endothelial cells, we demonstrate that IE isolated from Malawian paediatric CM cases showed increased binding to brain microvascular endothelial cells compared to IE from uncomplicated malaria (UM) cases. Further, UM isolates showed significantly greater adhesion to dermal than to brain microvascular endothelial cells. The major mediator of parasite adhesion is P. falciparum erythrocyte membrane protein 1, encoded by var genes. Higher levels of var gene transcripts predicted to bind host endothelial protein C receptor (EPCR) and ICAM‐1 were detected in CM isolates. These data provide further evidence for differential tissue binding in severe and uncomplicated malaria syndromes, and give additional support to the hypothesis that CM pathology is based on increased cytoadherence of IE in the brain microvasculature.

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Section: Binding To Microvascular Endothelial Cells Under Flowmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cerebral malaria is associated with differential cytoadherence to brain endothelial cells

et al. 2019

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“…Plasmodium falciparum was cultured as described previously 16,17 . Cultures were grown in RPMI-1640 supplemented with 24mM sodium bicarbonate (Sigma-Aldrich, St Louis, MO, USA) and 10% human serum (Interstate Blood Bank Inc, Memphis, TN, USA).…”

Section: Methodsmentioning

confidence: 99%

Developing a xenograft model of human vasculature in the mouse ear pinna

Meehan

Scales

Osii

et al. 2019

Preprint

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Humanised xenograft models allow for the analysis of human tissue within a physiological environment in vivo. However, current models often rely on the angiogenesis and ingrowth of recipient vasculature to perfuse tissues, preventing analysis of biological processes and diseases involving human blood vessels. This limits the effectiveness of xenografts in replicating human physiology and may lead to issues with translating findings into human research.We have designed a xenograft model of human vasculature to address this issue. Human subcutaneous fat was cultured in vitro to promote blood vessel outgrowth prior to implantation into immunocompromised mice. We demonstrate that implants survived, retained human vasculature and anastomosed with the circulatory system of the recipient mouse. Significantly, by performing transplants into the ear pinna, this system enabled intravital observation of xenografts by multiphoton microscopy, allowing us to visualise the steps leading to vascular cytoadherence of erythrocytes infected with the human parasite Plasmodium falciparum.This model represents a useful tool for imaging the interactions that occur within human tissues in vivo and permits visualization of blood flow and cellular recruitment in a system which is amenable to intervention for various studies in basic biology together with drug evaluation and mechanism of action studies.

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“…The culture-adapted ICAM-1-selected [19] parasite lines GL6, P069 and 8146 [19] were also investigated in reversal assays.…”

Section: Methodsmentioning

confidence: 99%

In vitro inhibition and reversal of Plasmodium falciparum cytoadherence to endothelium by monoclonal antibodies to ICAM-1 and CD36

Mustaffa

Storm

Whittaker

et al. 2017

Malar J

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BackgroundSequestration of parasitized red blood cells from the peripheral circulation during an infection with Plasmodium falciparum is caused by an interaction between the parasite protein PfEMP1 and receptors on the surface of host endothelial cells, known as cytoadherence. Several lines of evidence point to a link between the pathology of severe malaria and cytoadherence, therefore blocking adhesion receptors involved in this process could be a good target to inhibit pRBC sequestration and prevent disease. In a malaria endemic setting this is likely to be used as an adjunct therapy by reversing existing cytoadherence. Two well-characterized parasite lines plus three recently derived patient isolates were tested for their cytoadherence to purified receptors (CD36 and ICAM-1) as well as endothelial cells. Monoclonal antibodies against human CD36 and ICAM-1 were used to inhibit and reverse infected erythrocyte binding in static and flow-based adhesion assays.ResultsAnti-ICAM-1 and CD36 monoclonal antibodies were able to inhibit and reverse P. falciparum binding of lab and recently adapted patient isolates in vitro. However, reversal of binding was incomplete and varied in its efficiency between parasite isolates.ConclusionsThe results show that, as a proof of concept, disturbing existing ligand–receptor interactions is possible and could have potential therapeutic value for severe malaria. The variation seen in the degree of reversing existing binding with different parasite isolates and the incomplete nature of reversal, despite the use of high affinity inhibitors, suggest that anti-adhesion approaches as adjunct therapies for severe malaria may not be effective, and the focus may need to be on inhibitory approaches such as vaccines.

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An Analysis of the Binding Characteristics of a Panel of Recently Selected ICAM-1 Binding Plasmodium falciparum Patient Isolates

Cited by 21 publications

References 54 publications

Cerebral malaria is associated with differential cytoadherence to brain endothelial cells

Cerebral malaria is associated with differential cytoadherence to brain endothelial cells

Developing a xenograft model of human vasculature in the mouse ear pinna

In vitro inhibition and reversal of Plasmodium falciparum cytoadherence to endothelium by monoclonal antibodies to ICAM-1 and CD36

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