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Infection and Immunity, October 2006, p. 5487-5496, Vol. 74, No. 10
0019-9567/06/$08.00+0     doi:10.1128/IAI.01934-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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

Françoise Debierre-Grockiego,^1* Louis Schofield,² Nahid Azzouz,^1, Jörg Schmidt,¹ Cristiana Santos de Macedo,^1, Michael A. J. Ferguson,³ and Ralph T. Schwarz^1,4

Institut für Virologie, AG Parasitologie, Hans-Meerwein Strasse 2, D-35043 Marburg, Germany,¹ Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia,² Division of Biological Chemistry and Molecular Microbiology, The University of Dundee, DD1 5EH Dundee, Scotland, United Kingdom,³ 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, France⁴

Received 25 November 2005/ Returned for modification 22 February 2006/ Accepted 10 July 2006

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-) 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- 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.

Editor: J. F. Urban, Jr.

Present address: Laboratory for Organic Chemistry, ETH, Wolfgang-Pauli-Str. 10, CH-8093 Zurich, Switzerland.

Present address: UNIDERP-Rua Ceará, 333-CEP 79003-010 Campo Grande, MS, Brazil.

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