| Metabolic acidosis induced by Plasmodium falciparum intraerythrocytic stages alters blood-brain barrier integrity. | |
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MedLine Citation:
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PMID: 20683453 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The pathogenesis of cerebral malaria (CM) remains largely unknown. There is growing evidence that combination of both parasite and host factors could be involved in blood-brain barrier (BBB) breakdown. However, lack of adequate in vitro model of human BBB so far hampered molecular studies. In this article, we propose the use of hCMEC/D3 cells, a well-established human cerebral microvascular endothelial cell (EC) line, to study BBB breakdown induced by Plasmodium falciparum-parasitized red blood cells and environmental conditions. We show that coculture of parasitized erythrocytes with hCMEC/D3 cells induces cell adhesion and paracellular permeability increase, which correlates with disorganization of zonula occludens protein 1 expression pattern. Permeability increase and modification of tight junction proteins distribution are cytoadhesion independent. Finally, we show that permeability of hCMEC/D3 cell monolayers is mediated through parasite induced metabolic acidosis, which in turns correlates with apoptosis of parasitized erythrocytes. This new coculture model represents a very useful tool, which will improve the knowledge of BBB breakdown and the development of adjuvant therapies, together with antiparasitic drugs. |
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Authors:
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Sergine Zougbédé; Florence Miller; Philippe Ravassard; Angelita Rebollo; Liliane Cicéron; Pierre-Olivier Couraud; Dominique Mazier; Alicia Moreno |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-08-04 |
Journal Detail:
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Title: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Volume: 31 ISSN: 1559-7016 ISO Abbreviation: J. Cereb. Blood Flow Metab. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-02-04 Completed Date: 2011-03-17 Revised Date: 2012-02-01 |
Medline Journal Info:
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Nlm Unique ID: 8112566 Medline TA: J Cereb Blood Flow Metab Country: United States |
Other Details:
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Languages: eng Pagination: 514-26 Citation Subset: IM |
Affiliation:
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INSERM, UMRS 945, Paris, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acidosis
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metabolism*,
parasitology* Annexin A5 / metabolism Blood-Brain Barrier / parasitology* Cell Adhesion / drug effects Cell Line Endothelial Cells / physiology Erythrocytes / parasitology* Flow Cytometry Humans Hydrogen-Ion Concentration L-Lactate Dehydrogenase / metabolism Lentivirus / genetics Malaria, Cerebral / blood*, parasitology* Malaria, Falciparum / blood*, parasitology* Merozoites / parasitology, physiology Microscopy, Confocal Permeability Plasmodium falciparum* RNA Interference Tight Junctions / metabolism Transduction, Genetic Trypsin / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Annexin A5; EC 1.1.1.27/L-Lactate Dehydrogenase; EC 3.4.21.4/Trypsin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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