Submitted on March 7, 2006
Revised on April 3, 2006
Accepted on April 10, 2006
Interplay between lipoproteins and bee venom phospholipase A2 in relation to their anti-plasmodium toxicity
Carole Guillaume, Catherine Calzada, Michel Lagarde, Joseph Schrével, and Christiane Deregnaucourt
USM 0504, Muséum National d'Histoire Naturelle, Paris, Cedex 05 7523
Corresponding Author: deregnau{at}mnhn.fr
We previously showed that the in vitro intraerythrocytic development of the malarial agent Plasmodium falciparum is strongly inhibited by secreted phospholipases A2 (sPLA2s) from animal venoms. Inhibition is dependent on enzymatic activity and requires the presence of serum lipoproteins in the parasite culture medium. To evaluate the potential involvement of host lipoproteins and sPLA2s in malaria, we investigated the interactions between bee venom PLA2 (bvPLA2), human triglyceride-rich lipoproteins and infected erythrocytes. Even at high enzyme concentration (100×IC50), bvPLA2 binding to Plasmodium-infected or normal erythrocytes was not detected. On the contrary, tight association to lipoproteins was observed through the formation of buoyant bvPLA2/lipoprotein complexes. Direct involvement of the hydrolysis lipid products in toxicity was demonstrated. Arachidonic acid (C20:4), linoleic acid (C18:2) and, to a lesser extent, docosahexaenoic acid (C22:6), appeared as the main actors of toxicity. Minimal oxidation of lipoproteins enhanced toxicity of the lipolysed particles and induced their interaction with infected or normal erythrocytes. Fresh or oxidized lipolysed lipoproteins induced the parasite degeneration without host cell membrane disruption, ruling out a possible membranolytic action of fatty acids or peroxidation products in the death process. In conclusion, our data enlighten on the capability of secreted PLA2s to exert cytotoxicity via the extracellular generation of toxic lipids, and raise the question of whether such mechanisms could be at play in pathophysiological situations like malaria.
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