Modification of host cell membrane lipid composition by the intra-erythrocytic human malaria parasite Plasmodium falciparum

Abstract

The phospholipid and fatty acid compositions of the host infected erythrocyte plasma membrane (IEPM) have been determined for erythrocytes infected with the human malaria parasite Plasmodium falciparum. IEPM were prepared by selective lysis of the host erythrocyte (but not of the parasite membranes) with 0.1% saponin, followed by differential centrifugation. The purity of the IEPM was determined by measuring the membrane-specific enzyme markers acetylcholinesterase, glutamate dehydrogenase and lactate dehydrogenase, and by immunoelectron microscopy using monoclonal antibodies specific for human erythrocyte glycophorin A (4E7) and for a 195 kDa parasite membrane glycoprotein (Pf6 3B10.1). Both approaches demonstrated that the host erythrocyte plasma membrane preparation was free from contamination by parasite membranes. During intra-erythrocytic development of the parasite, the phospholipid composition of the erythrocyte membrane was strikingly altered. IEPM contained more phosphatidylcholine (38.7% versus 31.7%) and phosphatidylinositol (2.1% versus 0.8%) and less sphingomyelin (14.6% versus 28.0%) than normal uninfected erythrocytes. Similar alterations in phospholipid composition were determined for erythrocyte membranes of parasitized cells isolated by an alternative method utilizing polycationic polyacrylamide microbeads (Affigel 731). The total fatty acid compositions of the major phospholipids in IEPM were determined by g.l.c. The percentage of polyunsaturated fatty acids in normal erythrocyte phospholipids (39.4%) was much higher than in phospholipids from purified parasites (23.3%) or IEPM (24.0%). The unsaturation index of phospholipids in IEPM was considerably lower than in uninfected erythrocytes (107.5 versus 161.0) and was very similar to that in purified parasites (107.5 versus 98.5). Large increases in palmitic acid (C16:0) (from 21.88% to 31.21%) and in oleic acid (C18:1) (from 14.64% to 24.60%), and major decreases in arachidonic acid (C20:4) (from 17.36% to 7.85%) and in docosahexaenoic acid (C22:6) (from 4.34% to 1.8%) occurred as a result of infection. The fatty acid profiles of individual phospholipid classes from IEPM resembled in many instances the fatty acid profiles of parasite phospholipids rather than those of uninfected erythrocytes. Analysis of IEPM from P. falciparum-infected erythrocytes (trophozoite stage) revealed that, during intra-erythrocytic maturation of the parasite, the host erythrocyte phospholipid composition was markedly refashioned. These alterations were not dependent on the method used to isolate the IEPM, with similar results obtained using either a saponin-lysis method or binding to Affigel beads. Since mature erythrocytes have negligible lipid synthesis and metabolism, these alterations must occur as a result of parasite-directed metabolism of erythrocyte lipids and/or trafficking of lipids between the parasite and erythrocyte membranes.

Developmental-stage-specific triacylglycerol biosynthesis, degradation and trafficking as lipid bodies inPlasmodium falciparum-infected erythrocytes

“…As shown in Table 1, the lipid content of mature stage parasitized erythrocyte agrees with that reported previously Hsiao et al, 1991;Vial and Ancelin, 1998). PLs accumulated during parasite maturation accounts for 65-70% of the total lipids associated with infected erythrocyte.…”

Antimalarial properties of n-3 and n-6 polyunsaturated fatty acids: in vitro effects on Plasmodium falciparum and in vivo effects on P. berghei.

“…Under the influence of the parasite, host RBC cell membrane is grossly altered in structure and composition. Radiolabeled studies have shown that the uptake of certain fatty acids increases dramatically after the infection with malaria parasites (27)(28)(29)(30). Interestingly, malaria infection causes a marked reduction in the unsaturation index of RBC phospholipids, mainly as a result of the decreases in the amounts of C22:6,3, nC204n^a nd C182,n6 (27).…”

Interplay between lipoproteins and bee venom phospholipase A2 in relation to their anti-plasmodium toxicity

“…However, some considerations can be put forward: First, the external leaflet of the erythrocyte membrane is enriched in SM (38), whereas the lipoprotein surface is not, and SM was shown to inhibit sPLA 2 activity by perturbing the enzyme anchorage to the membrane (39). Second, the erythrocyte membrane is largely composed of proteins and glycoproteins that might prevent optimal binding of the enzyme.…”