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Fatty Acids from Plasmodium falciparum Down-Regulate the Toxic Activity of Malaria Glycosylphosphatidylinositols

Identifieur interne : 000F92 ( Pmc/Corpus ); précédent : 000F91; suivant : 000F93

Fatty Acids from Plasmodium falciparum Down-Regulate the Toxic Activity of Malaria Glycosylphosphatidylinositols

Auteurs : Françoise Debierre-Grockiego ; Louis Schofield ; Nahid Azzouz ; Jörg Schmidt ; Cristiana Santos De Macedo ; Michael A. J. Ferguson ; Ralph T. Schwarz

Source :

Infection and Immunity [ 0019-9567 ] ; 2006.

RBID : PMC:1594897

Abstract

Plasmodium falciparum malaria kills roughly 2.5 million people, mainly children, annually. Much of this mortality is thought to arise from the actions of a malarial toxin. This toxin, identified as glycosylphosphatidylinositol (GPI), is a major pathogenicity determinant in malaria. A malarial molecule, Pfj, labeled by [³H]glucosamine like the GPIs, was identified as a non-GPI molecule. Here we show that Pfj is able to down-regulate tumor necrosis factor alpha (TNF-α) production induced by the GPI of P. falciparum. Mass spectrometry analysis showed that Pfj was not a single molecule but represented a number of molecules. Separation methods, such as cation-exchange chromatography and thin-layer chromatography, were used to isolate and identify the following four main fatty acids responsible for the inhibitory effect on TNF-α production: myristic, pentadecanoic, palmitic, and palmitoleic acids. This regulatory effect on cytokine production suggests that there is balanced bioactivity for the different categories of malarial lipids.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1594897

DOI: 10.1128/IAI.01934-05
PubMed: 16988223
PubMed Central: 1594897

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PMC:1594897

Le document en format XML

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 Down-Regulate the Toxic Activity of Malaria Glycosylphosphatidylinositols </title>
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<author><name sortKey="Santos De Macedo, Cristiana" sort="Santos De Macedo, Cristiana" uniqKey="Santos De Macedo C" first="Cristiana" last="Santos De Macedo">Cristiana Santos De Macedo</name>
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<author><name sortKey="Ferguson, Michael A J" sort="Ferguson, Michael A J" uniqKey="Ferguson M" first="Michael A. J." last="Ferguson">Michael A. J. Ferguson</name>
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<author><name sortKey="Schwarz, Ralph T" sort="Schwarz, Ralph T" uniqKey="Schwarz R" first="Ralph T." last="Schwarz">Ralph T. Schwarz</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Fatty Acids from <italic>Plasmodium falciparum</italic>
 Down-Regulate the Toxic Activity of Malaria Glycosylphosphatidylinositols </title>
<author><name sortKey="Debierre Grockiego, Francoise" sort="Debierre Grockiego, Francoise" uniqKey="Debierre Grockiego F" first="Françoise" last="Debierre-Grockiego">Françoise Debierre-Grockiego</name>
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<author><name sortKey="Schofield, Louis" sort="Schofield, Louis" uniqKey="Schofield L" first="Louis" last="Schofield">Louis Schofield</name>
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<author><name sortKey="Azzouz, Nahid" sort="Azzouz, Nahid" uniqKey="Azzouz N" first="Nahid" last="Azzouz">Nahid Azzouz</name>
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<author><name sortKey="Schmidt, Jorg" sort="Schmidt, Jorg" uniqKey="Schmidt J" first="Jörg" last="Schmidt">Jörg Schmidt</name>
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<author><name sortKey="Santos De Macedo, Cristiana" sort="Santos De Macedo, Cristiana" uniqKey="Santos De Macedo C" first="Cristiana" last="Santos De Macedo">Cristiana Santos De Macedo</name>
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<author><name sortKey="Ferguson, Michael A J" sort="Ferguson, Michael A J" uniqKey="Ferguson M" first="Michael A. J." last="Ferguson">Michael A. J. Ferguson</name>
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<author><name sortKey="Schwarz, Ralph T" sort="Schwarz, Ralph T" uniqKey="Schwarz R" first="Ralph T." last="Schwarz">Ralph T. Schwarz</name>
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<series><title level="j">Infection and Immunity</title>
<idno type="ISSN">0019-9567</idno>
<idno type="eISSN">1098-5522</idno>
<imprint><date when="2006">2006</date>
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<front><div type="abstract" xml:lang="en"><p><italic>Plasmodium falciparum</italic>
 malaria kills roughly 2.5 million people, mainly children, annually. Much of this mortality is thought to arise from the actions of a malarial toxin. This toxin, identified as glycosylphosphatidylinositol (GPI), is a major pathogenicity determinant in malaria. A malarial molecule, Pfj, labeled by [<sup>3</sup>
H]glucosamine like the GPIs, was identified as a non-GPI molecule. Here we show that Pfj is able to down-regulate tumor necrosis factor alpha (TNF-α) production induced by the GPI of <italic>P. falciparum</italic>
. Mass spectrometry analysis showed that Pfj was not a single molecule but represented a number of molecules. Separation methods, such as cation-exchange chromatography and thin-layer chromatography, were used to isolate and identify the following four main fatty acids responsible for the inhibitory effect on TNF-α production: myristic, pentadecanoic, palmitic, and palmitoleic acids. This regulatory effect on cytokine production suggests that there is balanced bioactivity for the different categories of malarial lipids.</p>
</div>
</front>
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<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
  <front><journal-meta><journal-id journal-id-type="nlm-ta">Infect Immun</journal-id>
<journal-id journal-id-type="publisher-id">iai</journal-id>
<journal-title>Infection and Immunity</journal-title>
<issn pub-type="ppub">0019-9567</issn>
<issn pub-type="epub">1098-5522</issn>
<publisher><publisher-name>American Society for Microbiology</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">16988223</article-id>
<article-id pub-id-type="pmc">1594897</article-id>
<article-id pub-id-type="publisher-id">1934-05</article-id>
<article-id pub-id-type="doi">10.1128/IAI.01934-05</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Cellular Microbiology: Pathogen-Host Cell Molecular Interactions</subject>
</subj-group>
</article-categories>
<title-group><article-title>Fatty Acids from <italic>Plasmodium falciparum</italic>
 Down-Regulate the Toxic Activity of Malaria Glycosylphosphatidylinositols </article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Debierre-Grockiego</surname>
<given-names>Françoise</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="corresp" rid="cor1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Schofield</surname>
<given-names>Louis</given-names>
</name>
<xref ref-type="aff" rid="aff1">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Azzouz</surname>
<given-names>Nahid</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="fn" rid="fn1">†</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Schmidt</surname>
<given-names>Jörg</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Santos de Macedo</surname>
<given-names>Cristiana</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="fn" rid="fn2">‡</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ferguson</surname>
<given-names>Michael A. J.</given-names>
</name>
<xref ref-type="aff" rid="aff1">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Schwarz</surname>
<given-names>Ralph T.</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="aff" rid="aff1">4</xref>
</contrib>
</contrib-group>
<aff id="aff1">Institut für Virologie, AG Parasitologie, Hans-Meerwein Strasse 2, D-35043 Marburg, Germany,<label>1</label>
 Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia,<label>2</label>
 Division of Biological Chemistry and Molecular Microbiology, The University of Dundee, DD1 5EH Dundee, Scotland, United Kingdom,<label>3</label>
 Unité de Glycobiologie Structurale et Fonctionnelle UMR CNRS/USTL no. 8576-IFR 118, Université des Sciences et Technologies de Lille C9, F-59655 Villeneuve D'Ascq, France<label>4</label>
</aff>
<author-notes><fn id="cor1"><label>*</label>
<p>Corresponding author. Mailing address: Institut für Virologie, AG Parasitologie, Hans-Meerwein-Str. 2, D-35043 Marburg, Germany. Phone: (49)-6421-28-65493. Fax: (49)-6421-28-68976. E-mail: <email>debierre@staff.uni-marburg.de</email>
.</p>
</fn>
<fn id="fn1"><label>†</label>
<p>Present address: Laboratory for Organic Chemistry, ETH, Wolfgang-Pauli-Str. 10, CH-8093 Zurich, Switzerland.</p>
</fn>
<fn id="fn2"><label>‡</label>
<p>Present address: UNIDERP-Rua Ceará, 333-CEP 79003-010 Campo Grande, MS, Brazil.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub"><month>10</month>
<year>2006</year>
</pub-date>
<volume>74</volume>
<issue>10</issue>
<fpage>5487</fpage>
<lpage>5496</lpage>
<history><date date-type="received"><day>25</day>
<month>11</month>
<year>2005</year>
</date>
<date date-type="rev-recd"><day>22</day>
<month>2</month>
<year>2006</year>
</date>
<date date-type="accepted"><day>10</day>
<month>7</month>
<year>2006</year>
</date>
</history>
<copyright-statement>Copyright © 2006, American Society for Microbiology</copyright-statement>
<copyright-year>2006</copyright-year>
<self-uri xlink:title="pdf" xlink:href="zii01006005487.pdf"></self-uri>
<abstract><p><italic>Plasmodium falciparum</italic>
 malaria kills roughly 2.5 million people, mainly children, annually. Much of this mortality is thought to arise from the actions of a malarial toxin. This toxin, identified as glycosylphosphatidylinositol (GPI), is a major pathogenicity determinant in malaria. A malarial molecule, Pfj, labeled by [<sup>3</sup>
H]glucosamine like the GPIs, was identified as a non-GPI molecule. Here we show that Pfj is able to down-regulate tumor necrosis factor alpha (TNF-α) production induced by the GPI of <italic>P. falciparum</italic>
. Mass spectrometry analysis showed that Pfj was not a single molecule but represented a number of molecules. Separation methods, such as cation-exchange chromatography and thin-layer chromatography, were used to isolate and identify the following four main fatty acids responsible for the inhibitory effect on TNF-α production: myristic, pentadecanoic, palmitic, and palmitoleic acids. This regulatory effect on cytokine production suggests that there is balanced bioactivity for the different categories of malarial lipids.</p>
</abstract>
</article-meta>
<notes><fn-group><fn><p><italic>Editor:</italic>
 J. F. Urban, Jr.</p>
</fn>
</fn-group>
</notes>
</front>
</pmc>
</record>

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Fatty Acids from Plasmodium falciparum Down-Regulate the Toxic Activity of Malaria Glycosylphosphatidylinositols

Fatty Acids from Plasmodium falciparum Down-Regulate the Toxic Activity of Malaria Glycosylphosphatidylinositols

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