Cytoadherence of plasmodium berghei-infected red blood cells to murine brain and lung microvascular endothelial cells in vitro

El-Assaad, F; Wheway, J; Mitchell, AJ; Lou, J; Hunt, NH; Combes, V; Grau, GER

Cytoadherence of plasmodium berghei-infected red blood cells to murine brain and lung microvascular endothelial cells in vitro

El-Assaad, F Wheway, J Mitchell, AJ Lou, J Hunt, NH Combes, V

Grau, GER

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Publication Type:: Journal Article
Citation:: Infection and Immunity, 2013, 81 (11), pp. 3984 - 3991
Issue Date:: 2013-11-01

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Field	Value	Language
dc.contributor.author	El-Assaad, F	en_US
dc.contributor.author	Wheway, J	en_US
dc.contributor.author	Mitchell, AJ	en_US
dc.contributor.author	Lou, J	en_US
dc.contributor.author	Hunt, NH	en_US
dc.contributor.author	Combes, V https://orcid.org/0000-0003-2178-3596	en_US
dc.contributor.author	Grau, GER	en_US
dc.date.issued	2013-11-01	en_US
dc.identifier.citation	Infection and Immunity, 2013, 81 (11), pp. 3984 - 3991	en_US
dc.identifier.issn	0019-9567	en_US
dc.identifier.uri	http://hdl.handle.net/10453/116208
dc.description.abstract	Sequestration of infected red blood cells (iRBC) within the cerebral and pulmonary microvasculature is a hallmark of human cerebral malaria (hCM). The interaction between iRBC and the endothelium in hCM has been studied extensively and is linked to the severity of malaria. Experimental CM (eCM) caused by Plasmodium berghei ANKA reproduces most features of hCM, although the sequestration of RBC infected by P. berghei ANKA (PbA-iRBC) has not been completely delineated. The role of PbAiRBC sequestration in the severity of eCM is not well characterized. Using static and flow cytoadherence assays, we provide the first direct in vitro evidence for the binding of PbA-iRBC to murine brain and lung microvascular endothelial cells (MVEC). We found that basal PbA-iRBC cytoadherence to MVECs was significantly higher than that of normal red blood cells (NRBC) and of RBC infected with P. berghei K173 (PbK173-iRBC), a strain that causes noncerebral malaria (NCM). MVEC prestimulation with tumor necrosis factor (TNF) failed to promote any further significant increase in mixed-stage iRBC adherence. Interestingly, enrichment of the blood for mature parasites significantly increased PbA-iRBC binding to the MVECs prestimulated with TNF, while blockade of VCAM-1 reduced this adhesion. Our study provides evidence for the firm, flow-resistant binding to endothelial cells of iRBC from strain ANKA-infected mice, which develop CM, and for less binding of iRBC from strain K173-infected mice, which develop NCM. An understanding of P. berghei cytoadherence may help elucidate the importance of sequestration in the development of CM and aid the development of antibinding therapies to help reduce the burden of this syndrome. © 2013, American Society for Microbiology.	en_US
dc.relation.ispartof	Infection and Immunity	en_US
dc.relation.isbasedon	10.1128/IAI.00428-13	en_US
dc.subject.classification	Microbiology	en_US
dc.subject.mesh	Lung	en_US
dc.subject.mesh	Brain	en_US
dc.subject.mesh	Erythrocytes	en_US
dc.subject.mesh	Cells, Cultured	en_US
dc.subject.mesh	Endothelial Cells	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice, Inbred CBA	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Plasmodium berghei	en_US
dc.subject.mesh	Cell Adhesion	en_US
dc.subject.mesh	Female	en_US
dc.title	Cytoadherence of plasmodium berghei-infected red blood cells to murine brain and lung microvascular endothelial cells in vitro	en_US
dc.type	Journal Article
utslib.citation.volume	11	en_US
utslib.citation.volume	81	en_US
utslib.for	060502 Infectious Agents	en_US
utslib.for	06 Biological Sciences	en_US
utslib.for	07 Agricultural and Veterinary Sciences	en_US
utslib.for	11 Medical and Health Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access
pubs.issue	11	en_US
pubs.publication-status	Published	en_US
pubs.volume	81	en_US

Abstract:

Sequestration of infected red blood cells (iRBC) within the cerebral and pulmonary microvasculature is a hallmark of human cerebral malaria (hCM). The interaction between iRBC and the endothelium in hCM has been studied extensively and is linked to the severity of malaria. Experimental CM (eCM) caused by Plasmodium berghei ANKA reproduces most features of hCM, although the sequestration of RBC infected by P. berghei ANKA (PbA-iRBC) has not been completely delineated. The role of PbAiRBC sequestration in the severity of eCM is not well characterized. Using static and flow cytoadherence assays, we provide the first direct in vitro evidence for the binding of PbA-iRBC to murine brain and lung microvascular endothelial cells (MVEC). We found that basal PbA-iRBC cytoadherence to MVECs was significantly higher than that of normal red blood cells (NRBC) and of RBC infected with P. berghei K173 (PbK173-iRBC), a strain that causes noncerebral malaria (NCM). MVEC prestimulation with tumor necrosis factor (TNF) failed to promote any further significant increase in mixed-stage iRBC adherence. Interestingly, enrichment of the blood for mature parasites significantly increased PbA-iRBC binding to the MVECs prestimulated with TNF, while blockade of VCAM-1 reduced this adhesion. Our study provides evidence for the firm, flow-resistant binding to endothelial cells of iRBC from strain ANKA-infected mice, which develop CM, and for less binding of iRBC from strain K173-infected mice, which develop NCM. An understanding of P. berghei cytoadherence may help elucidate the importance of sequestration in the development of CM and aid the development of antibinding therapies to help reduce the burden of this syndrome. © 2013, American Society for Microbiology.

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http://hdl.handle.net/10453/116208