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Platelets Alter Gene Expression Profile in Human Brain Endothelial Cells in an In Vitro Model of Cerebral Malaria

Identifieur interne : 002A56 ( Pmc/Curation ); précédent : 002A55; suivant : 002A57

Platelets Alter Gene Expression Profile in Human Brain Endothelial Cells in an In Vitro Model of Cerebral Malaria

Auteurs : Mathieu Barbier [France] ; Dorothée Faille [France, Australie] ; Béatrice Loriod [France] ; Julien Textoris [France] ; Claire Camus [France] ; Denis Puthier [France] ; Laurence Flori [France] ; Samuel Crocodile Wassmer [États-Unis] ; Geneviève Victorero [France] ; Marie-Christine Alessi [France] ; Thierry Fusaï [France] ; Catherine Nguyen [France] ; Georges E. Grau [Australie] ; Pascal Rihet [France]

Source :

RBID : PMC:3095604

Abstract

Platelet adhesion to the brain microvasculature has been associated with cerebral malaria (CM) in humans, suggesting that platelets play a role in the pathogenesis of this syndrome. In vitro co-cultures have shown that platelets can act as a bridge between Plasmodium falciparum-infected red blood cells (pRBC) and human brain microvascular endothelial cells (HBEC) and potentiate HBEC apoptosis. Using cDNA microarray technology, we analyzed transcriptional changes of HBEC in response to platelets in the presence or the absence of tumor necrosis factor (TNF) and pRBC, which have been reported to alter gene expression in endothelial cells. Using a rigorous statistical approach with multiple test corrections, we showed a significant effect of platelets on gene expression in HBEC. We also detected a strong effect of TNF, whereas there was no transcriptional change induced specifically by pRBC. Nevertheless, a global ANOVA and a two-way ANOVA suggested that pRBC acted in interaction with platelets and TNF to alter gene expression in HBEC. The expression of selected genes was validated by RT-qPCR. The analysis of gene functional annotation indicated that platelets induce the expression of genes involved in inflammation and apoptosis, such as genes involved in chemokine-, TREM1-, cytokine-, IL10-, TGFβ-, death-receptor-, and apoptosis-signaling. Overall, our results support the hypothesis that platelets play a pathogenic role in CM.


Url:
DOI: 10.1371/journal.pone.0019651
PubMed: 21603600
PubMed Central: 3095604

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PMC:3095604

Le document en format XML

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<name sortKey="Victorero, Genevieve" sort="Victorero, Genevieve" uniqKey="Victorero G" first="Geneviève" last="Victorero">Geneviève Victorero</name>
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<name sortKey="Nguyen, Catherine" sort="Nguyen, Catherine" uniqKey="Nguyen C" first="Catherine" last="Nguyen">Catherine Nguyen</name>
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<name sortKey="Rihet, Pascal" sort="Rihet, Pascal" uniqKey="Rihet P" first="Pascal" last="Rihet">Pascal Rihet</name>
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<addr-line>Laboratoire de Pharmacogenétique des Maladies Parasitaires-EA 864, IFR 48, Faculté de Pharmacie, Aix-Marseille Université, Marseille, France</addr-line>
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<title xml:lang="en" level="a" type="main">Platelets Alter Gene Expression Profile in Human Brain Endothelial Cells in an
<italic>In Vitro</italic>
Model of Cerebral Malaria</title>
<author>
<name sortKey="Barbier, Mathieu" sort="Barbier, Mathieu" uniqKey="Barbier M" first="Mathieu" last="Barbier">Mathieu Barbier</name>
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<name sortKey="Faille, Dorothee" sort="Faille, Dorothee" uniqKey="Faille D" first="Dorothée" last="Faille">Dorothée Faille</name>
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<addr-line>Unité de Recherche en Biologie et en Épidémiologie Parasitaires, UMR 6236-URMITE-IMTSSA, Institut de Recherche Biomédicale des Armées-Antenne Marseille, Marseille, France</addr-line>
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<country xml:lang="fr">France</country>
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<addr-line>INSERM, UMR 626, Faculté de Médecine, Aix-Marseille Université, Marseille, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM, UMR 626, Faculté de Médecine, Aix-Marseille Université, Marseille</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff6">
<addr-line>Vascular Immunology Unit, Department of Pathology, University of Sydney, Camperdown, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Vascular Immunology Unit, Department of Pathology, University of Sydney, Camperdown</wicri:regionArea>
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<name sortKey="Loriod, Beatrice" sort="Loriod, Beatrice" uniqKey="Loriod B" first="Béatrice" last="Loriod">Béatrice Loriod</name>
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<addr-line>INSERM U928-TAGC, Aix-Marseille Université, IFR137, Marseille, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
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<name sortKey="Textoris, Julien" sort="Textoris, Julien" uniqKey="Textoris J" first="Julien" last="Textoris">Julien Textoris</name>
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<addr-line>INSERM U928-TAGC, Aix-Marseille Université, IFR137, Marseille, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
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</affiliation>
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<name sortKey="Camus, Claire" sort="Camus, Claire" uniqKey="Camus C" first="Claire" last="Camus">Claire Camus</name>
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<addr-line>Laboratoire de Pharmacogenétique des Maladies Parasitaires-EA 864, IFR 48, Faculté de Pharmacie, Aix-Marseille Université, Marseille, France</addr-line>
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<name sortKey="Puthier, Denis" sort="Puthier, Denis" uniqKey="Puthier D" first="Denis" last="Puthier">Denis Puthier</name>
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<addr-line>INSERM U928-TAGC, Aix-Marseille Université, IFR137, Marseille, France</addr-line>
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<name sortKey="Flori, Laurence" sort="Flori, Laurence" uniqKey="Flori L" first="Laurence" last="Flori">Laurence Flori</name>
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</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Laboratoire de Génétique Animale et Biologie Intégrative, Domaine de Vilvert, INRA AgroParisTech, Jouy-en-Josas</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Wassmer, Samuel Crocodile" sort="Wassmer, Samuel Crocodile" uniqKey="Wassmer S" first="Samuel Crocodile" last="Wassmer">Samuel Crocodile Wassmer</name>
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<addr-line>Department of Medical Parasitology, New York University School of Medicine, New York, New York, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Medical Parasitology, New York University School of Medicine, New York, New York</wicri:regionArea>
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<name sortKey="Victorero, Genevieve" sort="Victorero, Genevieve" uniqKey="Victorero G" first="Geneviève" last="Victorero">Geneviève Victorero</name>
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<addr-line>INSERM U928-TAGC, Aix-Marseille Université, IFR137, Marseille, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM U928-TAGC, Aix-Marseille Université, IFR137, Marseille</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Alessi, Marie Christine" sort="Alessi, Marie Christine" uniqKey="Alessi M" first="Marie-Christine" last="Alessi">Marie-Christine Alessi</name>
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<addr-line>INSERM, UMR 626, Faculté de Médecine, Aix-Marseille Université, Marseille, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM, UMR 626, Faculté de Médecine, Aix-Marseille Université, Marseille</wicri:regionArea>
</affiliation>
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<name sortKey="Fusai, Thierry" sort="Fusai, Thierry" uniqKey="Fusai T" first="Thierry" last="Fusaï">Thierry Fusaï</name>
<affiliation wicri:level="1">
<nlm:aff id="aff3">
<addr-line>Unité de Recherche en Biologie et en Épidémiologie Parasitaires, UMR 6236-URMITE-IMTSSA, Institut de Recherche Biomédicale des Armées-Antenne Marseille, Marseille, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Unité de Recherche en Biologie et en Épidémiologie Parasitaires, UMR 6236-URMITE-IMTSSA, Institut de Recherche Biomédicale des Armées-Antenne Marseille, Marseille</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Nguyen, Catherine" sort="Nguyen, Catherine" uniqKey="Nguyen C" first="Catherine" last="Nguyen">Catherine Nguyen</name>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<addr-line>INSERM U928-TAGC, Aix-Marseille Université, IFR137, Marseille, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM U928-TAGC, Aix-Marseille Université, IFR137, Marseille</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Grau, Georges E" sort="Grau, Georges E" uniqKey="Grau G" first="Georges E." last="Grau">Georges E. Grau</name>
<affiliation wicri:level="1">
<nlm:aff id="aff6">
<addr-line>Vascular Immunology Unit, Department of Pathology, University of Sydney, Camperdown, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Vascular Immunology Unit, Department of Pathology, University of Sydney, Camperdown</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Rihet, Pascal" sort="Rihet, Pascal" uniqKey="Rihet P" first="Pascal" last="Rihet">Pascal Rihet</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<addr-line>Laboratoire de Pharmacogenétique des Maladies Parasitaires-EA 864, IFR 48, Faculté de Pharmacie, Aix-Marseille Université, Marseille, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Laboratoire de Pharmacogenétique des Maladies Parasitaires-EA 864, IFR 48, Faculté de Pharmacie, Aix-Marseille Université, Marseille</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<addr-line>INSERM U928-TAGC, Aix-Marseille Université, IFR137, Marseille, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM U928-TAGC, Aix-Marseille Université, IFR137, Marseille</wicri:regionArea>
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<series>
<title level="j">PLoS ONE</title>
<idno type="eISSN">1932-6203</idno>
<imprint>
<date when="2011">2011</date>
</imprint>
</series>
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</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p>Platelet adhesion to the brain microvasculature has been associated with cerebral malaria (CM) in humans, suggesting that platelets play a role in the pathogenesis of this syndrome.
<italic>In vitro</italic>
co-cultures have shown that platelets can act as a bridge between
<italic>Plasmodium falciparum</italic>
-infected red blood cells (pRBC) and human brain microvascular endothelial cells (HBEC) and potentiate HBEC apoptosis. Using cDNA microarray technology, we analyzed transcriptional changes of HBEC in response to platelets in the presence or the absence of tumor necrosis factor (TNF) and pRBC, which have been reported to alter gene expression in endothelial cells. Using a rigorous statistical approach with multiple test corrections, we showed a significant effect of platelets on gene expression in HBEC. We also detected a strong effect of TNF, whereas there was no transcriptional change induced specifically by pRBC. Nevertheless, a global ANOVA and a two-way ANOVA suggested that pRBC acted in interaction with platelets and TNF to alter gene expression in HBEC. The expression of selected genes was validated by RT-qPCR. The analysis of gene functional annotation indicated that platelets induce the expression of genes involved in inflammation and apoptosis, such as genes involved in chemokine-, TREM1-, cytokine-, IL10-, TGFβ-, death-receptor-, and apoptosis-signaling. Overall, our results support the hypothesis that platelets play a pathogenic role in CM.</p>
</div>
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<pmc article-type="research-article">
<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">PLoS One</journal-id>
<journal-id journal-id-type="publisher-id">plos</journal-id>
<journal-id journal-id-type="pmc">plosone</journal-id>
<journal-title-group>
<journal-title>PLoS ONE</journal-title>
</journal-title-group>
<issn pub-type="epub">1932-6203</issn>
<publisher>
<publisher-name>Public Library of Science</publisher-name>
<publisher-loc>San Francisco, USA</publisher-loc>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">21603600</article-id>
<article-id pub-id-type="pmc">3095604</article-id>
<article-id pub-id-type="publisher-id">PONE-D-11-00105</article-id>
<article-id pub-id-type="doi">10.1371/journal.pone.0019651</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Research Article</subject>
</subj-group>
<subj-group subj-group-type="Discipline-v2">
<subject>Biology</subject>
<subj-group>
<subject>Genetics</subject>
<subj-group>
<subject>Gene Networks</subject>
</subj-group>
</subj-group>
<subj-group>
<subject>Genomics</subject>
<subj-group>
<subject>Genome Analysis Tools</subject>
<subj-group>
<subject>Gene Ontologies</subject>
<subject>Genetic Networks</subject>
<subject>Transcriptomes</subject>
</subj-group>
</subj-group>
<subj-group>
<subject>Genome Expression Analysis</subject>
</subj-group>
</subj-group>
<subj-group>
<subject>Immunology</subject>
<subj-group>
<subject>Immunity</subject>
<subj-group>
<subject>Inflammation</subject>
</subj-group>
</subj-group>
<subj-group>
<subject>Immune Response</subject>
<subject>Immunopathology</subject>
</subj-group>
</subj-group>
<subj-group>
<subject>Microbiology</subject>
<subj-group>
<subject>Immunity</subject>
<subj-group>
<subject>Inflammation</subject>
</subj-group>
</subj-group>
<subj-group>
<subject>Host-Pathogen Interaction</subject>
<subject>Parasitology</subject>
<subject>Pathogenesis</subject>
</subj-group>
</subj-group>
<subj-group>
<subject>Molecular Cell Biology</subject>
<subj-group>
<subject>Cellular Types</subject>
<subj-group>
<subject>Endothelial Cells</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v2">
<subject>Medicine</subject>
<subj-group>
<subject>Hematology</subject>
<subj-group>
<subject>Platelets</subject>
</subj-group>
</subj-group>
<subj-group>
<subject>Infectious Diseases</subject>
<subj-group>
<subject>Parasitic Diseases</subject>
<subj-group>
<subject>Malaria</subject>
<subj-group>
<subject>Plasmodium Falciparum</subject>
</subj-group>
</subj-group>
</subj-group>
<subj-group>
<subject>Tropical Diseases (Non-Neglected)</subject>
<subj-group>
<subject>Malaria</subject>
<subj-group>
<subject>Plasmodium Falciparum</subject>
</subj-group>
</subj-group>
</subj-group>
<subj-group>
<subject>Infectious Diseases of the Nervous System</subject>
</subj-group>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Platelets Alter Gene Expression Profile in Human Brain Endothelial Cells in an
<italic>In Vitro</italic>
Model of Cerebral Malaria</article-title>
<alt-title alt-title-type="running-head">Platelets Alter Endothelial Transcriptome in CM</alt-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Barbier</surname>
<given-names>Mathieu</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="author-notes" rid="fn1">
<sup>¤</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Faille</surname>
<given-names>Dorothée</given-names>
</name>
<xref ref-type="aff" rid="aff3">
<sup>3</sup>
</xref>
<xref ref-type="aff" rid="aff4">
<sup>4</sup>
</xref>
<xref ref-type="aff" rid="aff6">
<sup>6</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Loriod</surname>
<given-names>Béatrice</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Textoris</surname>
<given-names>Julien</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Camus</surname>
<given-names>Claire</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Puthier</surname>
<given-names>Denis</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Flori</surname>
<given-names>Laurence</given-names>
</name>
<xref ref-type="aff" rid="aff5">
<sup>5</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wassmer</surname>
<given-names>Samuel Crocodile</given-names>
</name>
<xref ref-type="aff" rid="aff7">
<sup>7</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Victorero</surname>
<given-names>Geneviève</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Alessi</surname>
<given-names>Marie-Christine</given-names>
</name>
<xref ref-type="aff" rid="aff4">
<sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Fusaï</surname>
<given-names>Thierry</given-names>
</name>
<xref ref-type="aff" rid="aff3">
<sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Nguyen</surname>
<given-names>Catherine</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Grau</surname>
<given-names>Georges E.</given-names>
</name>
<xref ref-type="aff" rid="aff6">
<sup>6</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Rihet</surname>
<given-names>Pascal</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
<xref ref-type="corresp" rid="cor1">
<sup>*</sup>
</xref>
</contrib>
</contrib-group>
<aff id="aff1">
<label>1</label>
<addr-line>Laboratoire de Pharmacogenétique des Maladies Parasitaires-EA 864, IFR 48, Faculté de Pharmacie, Aix-Marseille Université, Marseille, France</addr-line>
</aff>
<aff id="aff2">
<label>2</label>
<addr-line>INSERM U928-TAGC, Aix-Marseille Université, IFR137, Marseille, France</addr-line>
</aff>
<aff id="aff3">
<label>3</label>
<addr-line>Unité de Recherche en Biologie et en Épidémiologie Parasitaires, UMR 6236-URMITE-IMTSSA, Institut de Recherche Biomédicale des Armées-Antenne Marseille, Marseille, France</addr-line>
</aff>
<aff id="aff4">
<label>4</label>
<addr-line>INSERM, UMR 626, Faculté de Médecine, Aix-Marseille Université, Marseille, France</addr-line>
</aff>
<aff id="aff5">
<label>5</label>
<addr-line>Laboratoire de Génétique Animale et Biologie Intégrative, Domaine de Vilvert, INRA AgroParisTech, Jouy-en-Josas, France</addr-line>
</aff>
<aff id="aff6">
<label>6</label>
<addr-line>Vascular Immunology Unit, Department of Pathology, University of Sydney, Camperdown, Australia</addr-line>
</aff>
<aff id="aff7">
<label>7</label>
<addr-line>Department of Medical Parasitology, New York University School of Medicine, New York, New York, United States of America</addr-line>
</aff>
<contrib-group>
<contrib contrib-type="editor">
<name>
<surname>Paul</surname>
<given-names>Rick Edward</given-names>
</name>
<role>Editor</role>
<xref ref-type="aff" rid="edit1"></xref>
</contrib>
</contrib-group>
<aff id="edit1">Institut Pasteur, France</aff>
<author-notes>
<corresp id="cor1">* E-mail:
<email>rihet@tagc.univ-mrs.fr</email>
</corresp>
<fn fn-type="con">
<p>Wrote the paper: MB DF PR. Conceived the study and participated in its design and coordination: MB DF GEG PR. Provided material and analytical tools: M-CA TF SCW CN. Performed the co-cultures: DF. Performed RNA extraction: MB. Responsible for the design and production of the microarray and participated in the acquisition of microarray data: BL GV JT DP. Performed cDNA hybridization and acquisition of microarray data: MB CC. Performed data analysis: MB LF PR. All authors contributed to and approved the final manuscript.</p>
</fn>
<fn id="fn1" fn-type="current-aff">
<label>¤</label>
<p>Current address: UMR 745, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris Descartes, Paris, France</p>
</fn>
</author-notes>
<pub-date pub-type="collection">
<year>2011</year>
</pub-date>
<pub-date pub-type="epub">
<day>16</day>
<month>5</month>
<year>2011</year>
</pub-date>
<volume>6</volume>
<issue>5</issue>
<elocation-id>e19651</elocation-id>
<history>
<date date-type="received">
<day>21</day>
<month>12</month>
<year>2010</year>
</date>
<date date-type="accepted">
<day>12</day>
<month>4</month>
<year>2011</year>
</date>
</history>
<permissions>
<copyright-statement>Barbier et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</copyright-statement>
<copyright-year>2011</copyright-year>
</permissions>
<abstract>
<p>Platelet adhesion to the brain microvasculature has been associated with cerebral malaria (CM) in humans, suggesting that platelets play a role in the pathogenesis of this syndrome.
<italic>In vitro</italic>
co-cultures have shown that platelets can act as a bridge between
<italic>Plasmodium falciparum</italic>
-infected red blood cells (pRBC) and human brain microvascular endothelial cells (HBEC) and potentiate HBEC apoptosis. Using cDNA microarray technology, we analyzed transcriptional changes of HBEC in response to platelets in the presence or the absence of tumor necrosis factor (TNF) and pRBC, which have been reported to alter gene expression in endothelial cells. Using a rigorous statistical approach with multiple test corrections, we showed a significant effect of platelets on gene expression in HBEC. We also detected a strong effect of TNF, whereas there was no transcriptional change induced specifically by pRBC. Nevertheless, a global ANOVA and a two-way ANOVA suggested that pRBC acted in interaction with platelets and TNF to alter gene expression in HBEC. The expression of selected genes was validated by RT-qPCR. The analysis of gene functional annotation indicated that platelets induce the expression of genes involved in inflammation and apoptosis, such as genes involved in chemokine-, TREM1-, cytokine-, IL10-, TGFβ-, death-receptor-, and apoptosis-signaling. Overall, our results support the hypothesis that platelets play a pathogenic role in CM.</p>
</abstract>
<counts>
<page-count count="14"></page-count>
</counts>
</article-meta>
</front>
</pmc>
</record>

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