Fatty acids from Plasmodium falciparum down-regulate the toxic activity of malaria glycosylphosphatidylinositols.
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-alpha) 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-alpha 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.
Debierre-Grockiego
Françoise
F
Institut für Virologie, AG Parasitologie, Hans-Meerwein-Str. 2, D-35043 Marburg, Germany. debierre@staff.uni-marburg.de
Schofield
Louis
L
Azzouz
Nahid
N
Schmidt
Jörg
J
Santos de Macedo
Cristiana
C
Ferguson
Michael A J
MA
Schwarz
Ralph T
RT
D000818:Animals; D015536:Down-Regulation; D005227:Fatty Acids / Q000302:isolation & purification / Q000494:pharmacology*; D005229:Fatty Acids, Monounsaturated / Q000302:isolation & purification / Q000494:pharmacology; D017261:Glycosylphosphatidylinositols / Q000633:toxicity; D016778:Malaria, Falciparum / Q000276:immunology*; D013058:Mass Spectrometry; D051379:Mice; D008854:Microscopy, Electron; D019814:Myristic Acid / Q000302:isolation & purification / Q000494:pharmacology; D019308:Palmitic Acid / Q000302:isolation & purification / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000819:agonists / Q000037:antagonists & inhibitors*; D037521:Virulence Factors / Q000037:antagonists & inhibitors* / Q000633:toxicity
D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D017261:Glycosylphosphatidylinositols; D014409:Tumor Necrosis Factor-alpha; D037521:Virulence Factors; D019814:Myristic Acid; C008757:palmitoleic acid; D019308:Palmitic Acid; C117025:pentadecanoic acid