Cytoadherence and virulence - the case of <it>Plasmodium knowlesi </it>malaria

<p>Abstract</p> <p>Background</p> <p>Cytoadherence of infected red blood cells to brain endothelium is causally implicated in malarial coma, one of the severe manifestations of falciparum malaria. Cytoadherence is mediated by specific binding of variant parasite antigen...

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Main Authors: Fatih Farrah A, Siner Angela, Ahmed Atique, Woon Lu, Craig Alister G, Singh Balbir, Krishna Sanjeev, Cox-Singh Janet
Format: Article
Language:English
Published: BMC 2012-02-01
Series:Malaria Journal
Subjects:
Online Access:http://www.malariajournal.com/content/11/1/33
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author Fatih Farrah A
Siner Angela
Ahmed Atique
Woon Lu
Craig Alister G
Singh Balbir
Krishna Sanjeev
Cox-Singh Janet
author_facet Fatih Farrah A
Siner Angela
Ahmed Atique
Woon Lu
Craig Alister G
Singh Balbir
Krishna Sanjeev
Cox-Singh Janet
author_sort Fatih Farrah A
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Cytoadherence of infected red blood cells to brain endothelium is causally implicated in malarial coma, one of the severe manifestations of falciparum malaria. Cytoadherence is mediated by specific binding of variant parasite antigens, expressed on the surface of infected erythrocytes, to endothelial receptors including, ICAM-1, VCAM and CD36. In fatal cases of severe falciparum malaria with coma, blood vessels in the brain are characteristically congested with infected erythrocytes. Brain sections from a fatal case of knowlesi malaria, but without coma, were similarly congested with infected erythrocytes. The objective of this study was to determine the binding phenotype of <it>Plasmodium knowlesi </it>infected human erythrocytes to recombinant human ICAM-1, VCAM and CD36.</p> <p>Methods</p> <p>Five patients with PCR-confirmed <it>P. knowlesi </it>malaria were recruited into the study with consent between April and August 2010. Pre-treatment venous blood was washed and cultured <it>ex vivo </it>to increase the proportion of schizont-infected erythrocytes. Cultured blood was seeded into Petri dishes with triplicate areas coated with ICAM-1, VCAM and CD36. Following incubation at 37°C for one hour the dishes were washed and the number of infected erythrocytes bound/mm<sup>2 </sup>to PBS control areas and to recombinant human ICAM-1 VCAM and CD36 coated areas were recorded. Each assay was performed in duplicate. Assay performance was monitored with the <it>Plasmodium falciparum </it>clone HB3.</p> <p>Results</p> <p>Blood samples were cultured <it>ex vivo </it>for up to 14.5 h (mean 11.3 ± 1.9 h) to increase the relative proportion of mature trophozoite and schizont-infected red blood cells to at least 50% (mean 65.8 ± 17.51%). Three (60%) isolates bound significantly to ICAM-1 and VCAM, one (20%) isolate bound to VCAM and none of the five bound significantly to CD36.</p> <p>Conclusions</p> <p><it>Plasmodium knowlesi </it>infected erythrocytes from human subjects bind in a specific but variable manner to the inducible endothelial receptors ICAM-1 and VCAM. Binding to the constitutively-expressed endothelial receptor CD36 was not detected. Further work will be required to define the pathological consequences of these interactions.</p>
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spelling doaj.art-c963f8e756924f41a38f52fd408d27432022-12-21T22:02:11ZengBMCMalaria Journal1475-28752012-02-011113310.1186/1475-2875-11-33Cytoadherence and virulence - the case of <it>Plasmodium knowlesi </it>malariaFatih Farrah ASiner AngelaAhmed AtiqueWoon LuCraig Alister GSingh BalbirKrishna SanjeevCox-Singh Janet<p>Abstract</p> <p>Background</p> <p>Cytoadherence of infected red blood cells to brain endothelium is causally implicated in malarial coma, one of the severe manifestations of falciparum malaria. Cytoadherence is mediated by specific binding of variant parasite antigens, expressed on the surface of infected erythrocytes, to endothelial receptors including, ICAM-1, VCAM and CD36. In fatal cases of severe falciparum malaria with coma, blood vessels in the brain are characteristically congested with infected erythrocytes. Brain sections from a fatal case of knowlesi malaria, but without coma, were similarly congested with infected erythrocytes. The objective of this study was to determine the binding phenotype of <it>Plasmodium knowlesi </it>infected human erythrocytes to recombinant human ICAM-1, VCAM and CD36.</p> <p>Methods</p> <p>Five patients with PCR-confirmed <it>P. knowlesi </it>malaria were recruited into the study with consent between April and August 2010. Pre-treatment venous blood was washed and cultured <it>ex vivo </it>to increase the proportion of schizont-infected erythrocytes. Cultured blood was seeded into Petri dishes with triplicate areas coated with ICAM-1, VCAM and CD36. Following incubation at 37°C for one hour the dishes were washed and the number of infected erythrocytes bound/mm<sup>2 </sup>to PBS control areas and to recombinant human ICAM-1 VCAM and CD36 coated areas were recorded. Each assay was performed in duplicate. Assay performance was monitored with the <it>Plasmodium falciparum </it>clone HB3.</p> <p>Results</p> <p>Blood samples were cultured <it>ex vivo </it>for up to 14.5 h (mean 11.3 ± 1.9 h) to increase the relative proportion of mature trophozoite and schizont-infected red blood cells to at least 50% (mean 65.8 ± 17.51%). Three (60%) isolates bound significantly to ICAM-1 and VCAM, one (20%) isolate bound to VCAM and none of the five bound significantly to CD36.</p> <p>Conclusions</p> <p><it>Plasmodium knowlesi </it>infected erythrocytes from human subjects bind in a specific but variable manner to the inducible endothelial receptors ICAM-1 and VCAM. Binding to the constitutively-expressed endothelial receptor CD36 was not detected. Further work will be required to define the pathological consequences of these interactions.</p>http://www.malariajournal.com/content/11/1/33<it>P. knowlesi</it>CytoadherenceSICAvarICAM-1VCAMCD36MalariaComa
spellingShingle Fatih Farrah A
Siner Angela
Ahmed Atique
Woon Lu
Craig Alister G
Singh Balbir
Krishna Sanjeev
Cox-Singh Janet
Cytoadherence and virulence - the case of <it>Plasmodium knowlesi </it>malaria
Malaria Journal
<it>P. knowlesi</it>
Cytoadherence
SICAvar
ICAM-1
VCAM
CD36
Malaria
Coma
title Cytoadherence and virulence - the case of <it>Plasmodium knowlesi </it>malaria
title_full Cytoadherence and virulence - the case of <it>Plasmodium knowlesi </it>malaria
title_fullStr Cytoadherence and virulence - the case of <it>Plasmodium knowlesi </it>malaria
title_full_unstemmed Cytoadherence and virulence - the case of <it>Plasmodium knowlesi </it>malaria
title_short Cytoadherence and virulence - the case of <it>Plasmodium knowlesi </it>malaria
title_sort cytoadherence and virulence the case of it plasmodium knowlesi it malaria
topic <it>P. knowlesi</it>
Cytoadherence
SICAvar
ICAM-1
VCAM
CD36
Malaria
Coma
url http://www.malariajournal.com/content/11/1/33
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