Plasmodium falciparum infected red blood cells

Chakravorty, S. J., Carret, C., Nash, G. B., Ivens, A., Szestak, T., and Craig, A. G. (2007). Altered phenotype and gene transcription in endothelial cells, induced by Plasmodium falciparum-infected red blood cells Pathogenic or protective Int. J. Parasitol. 37,975-987. 

Cooke, B. M., Lingelbach, K., Bannister, L. H., and Tilley, L. (2004a). Protein trafficking in Plasmodium falciparum-infected red blood cells. Trends Parasitol. 20,581-589. 

Ginsburg, H., Kutner, S., Krugliak, M., and Cabantchik, Z. I. (1985). Characterization of permeation pathways appearing in the host membrane of Plasmodium falciparum infected red blood cells. Mol. Biochem. Parasitol. 14, 313-322. 

Luersen, K., Walter, R. D., and Muller, S. (2000). Plasmodium falciparum-infected red blood cells depend on a functional glutathione de novo synthesis attributable to an enhanced loss of glutathione. Biochem. ]. 346(Pt 2), 545-552. 

Grellier, P., Rigomier, D., Clavey, V., Fruchart, J.-C. and Schrevel, J. (1991) Lipid traffic between high density lipoproteins and Plasmodium falciparum-infected red blood cells. J. Cell Biol. 112 261-111. 

Adovelande J, Boulard Y, Berry J-P, Galle P, Slodzian G, Schrevel J. Detection and cartography of the fluorinated antimalarial drug mefloquine in normal and Plasmodium falciparum infected red blood cells by scanning ion microscopy and mass spectrometry. Biol Cell 1994 81 185-192. 

Over 100 Plasmodium species contribute to the spread of malaria, but only four of these (P. falciparum, P. vivax, P. ovale, and P. malariae) account for human infection, the deadliest being P. falciparum. The malaria life cycle exists first in a mosquito, and then it passes to a human host. An infected female Anopholes mosquito is the host of the parasite s sporogonic hfe cycle. Mature P. falciparum sporozoites reach the salivary glands of the mosquito, and the parasite is transmitted to a human host when the mosquito feeds. During this blood meal, sporozoites are released into the bloodstream where they penetrate hepatic cells and mature into schizonts. The liver cells rupture after approximately two weeks, discharging merozoites into the bloodstream whereupon they infect red blood cells (RBCs). Every 48 to 78 hours, mature merozoites rupture from... 

Rock, E. P., Roth, E. F., Jr., Rojas-Corona, R. R., Sherwood, J. A., Nagel, R. L., Howard, R. J., and Kaul, D. K. (1988). Thrombospondin mediates the cytoadherence of Plasmodium falciparum-infected red cells to vascular endothelium in shear flow conditions. Blood 71, 71-75. 

Waller, K. L., Nunomura, W., An, X., Cooke, B. M., Mohandas, N., and Coppel, R. L. (2003). Mature parasite-infected erythrocyte surface antigen (MESA) of Plasmodium falciparum binds to the 30-kDa domain of protein 4.1 in malaria-infected red blood cells. Blood 102, 1911-1914. 

Waterkeyn, J. G., Wickham, M. E., Davern, K. M., Cooke, B. M., Coppel, R. L., Reeder, J. C., Culvenor, J. G., Waller, R. F., and Cowman, A. F. (2000). Targeted mutagenesis of Plasmodium falciparum erythrocyte membrane protein 3 (PfEMP3) disrupts cytoadherence of malaria-infected red blood cells. EMBO ]. 19, 2813-2823. 

The most severe form of malaria is caused by Plasmodium falciparum and can be fatal. Fever occurs every third day due to rupture of infected red blood cells. Other forms are less severe and rarely fatal. 

Four different protozoa of the genus Plasmodium -P. falciparum, P. vivax, P. ovale and P malariae - can cause malaria. P. falciparum is the most virulent, being responsible for virtually all fatal malaria cases. Humans are infected by a feeding female Anopheles mosquito (Fig. 2). The clinical symptoms of malaria are associated with the development of the parasite within human red blood cells, while the liver stages remain asymptomatic. The following dtugs (in alphabetical order) are currently in use for the treatment of malaria [5]. 

Sickle cell gene mutation offers partial protection against serious malarial infection. Abnormal red blood cells (RBCs) are less easily parasitized by Plasmodium falciparum than normal RBCs. Consequently, persons with heterozygous sickle gene (SCT) have a selective advantage in regions (tropical areas) where malaria is endemic. The incidence of the sickle gene in a population correlates with the historical incidence of malaria. 

Roth, E. F., Jr., Schulman, S., Vanderberg, J., and Olson, J. (1986). Pathways for the reduction of oxidized glutathione in the Plasmodium falciparum-infected erythrocyte Can parasite enzymes replace host red cell glucose-6-phosphate dehydrogenase Blood 67,827-830. 

Staines, H. M., Ashmore, S., Felgate, H., Moore, J., Powell, T., and Ellory, J. C. (2006). Solute transport via the new permeability pathways in Plasmodium falciparum-infected human red blood cells is not consistent with a simple single-channel model. Blood 108,3187-3194. Staines, H. M., Ellory, J. C., and Kirk, K. (2001). Perturbation of the pump-leak balance for Na(+) and K(+) in malaria-infected erythrocytes. Am. J. Physiol. Cell Physiol. 280, C1576-C1587. 

Probably no disease has killed more humans throughout history than malaria. Malaria is transmitted by the bite of an Anopheles mosquito. There are four different parasites that can infect humans, but Plasmodium falciparum is the most virulent. The parasite first migrates to the liver where after several replications the parasites are released into the bloodstream. The parasite then invades the red blood cells and feeds off the hemoglobin. Survival of the parasite relies on the ability of the parasite to package the toxic heme metabolites formed during hemoglobin metabolism in nontoxic hemazoin particles. The parasite causes anemia, fevers, chills, veno-occlusive disorders, liver damage, and death. 

Within infected erythrocytes, Plasmodium falciparum (strain responsible for most fatal cases) digest fee host hemoglobin wife the aid of several specific parasite proteases 4, 5). Hemoglobin comprises 93% of fee cytosolic protein of red blood cells smd up to 80% of the 3 mM hemoglobin is degraded by fee parasite (6). This intensive proteolysis releases free heme and amino-acids. These amino-acids are incorporated into parasitic proteins and feis supply is essential for fee survival of Plasmodium, a "true parasite", which has a limited capacity for fee de novo amino-acid synthesis. Only a very limited amoimt of the free heme is metabolized by fee parasite as iron source. 

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