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Effect of intra-erythrocytic magnesium ions on invasion by Plasmodium falciparum

  • S. J. Field (a1), K. Rangachari (a1) (a2), A. R. Dluzewski (a1), R. J. M. Wilson (a2) and W. B. Gratzer (a1)...


Exclusion of magnesium ions from resealed ghosts or their extraction from intact human red cells by means of an ionophore results in a reversible drop in susceptibility to invasion by Plasmodium falciparum merozoites in vitro. Resealed ghosts, containing magnesium-ATP and diluted cytosol, are invaded with high efficiency only when the original hypotonic lysis is carried Out in the presence of magnesium ions. This effect is not related to the loss of membrane-associated constituents when magnesium ions are absent. Ghosts containing calcium ions, together with the protective agent, flunarizine, were essentially resistant to invasion; this effect is again at least partially reversible. A possible explanation of these phenomena is that entry of the merozoite may be inhibited by breakdown of the host cell phospholipid asymmetry, with the appearance of aminophospholipids at the outer cell surface.



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Backman, L. (1986). Shape control in the human red cell. Journal of Cell Science 80, 281–8.
Bitbol, M., Fellmann, P., Zachowski, A. & Devaux, P. F. (1987). Ion regulation of phosphatidylserine and phosphatidylethanolarnine outside-inside translocation in human erythrocytes. Biochimica et Biophysica Acta 904, 268–82.
Connor, J., Bucana, C., Fidler, I. J. & Schroit, A. J. (1989). Differentiation-dependent exposure of phosphatidylserine in mammalian plasma membranes: Quantitative assessment of outer-leaflet lipid by prothrombinase complex formation. Proceedings of the National Academy of Sciences, USA 86, 3184–8.
Connor, J., Gillum, K. & Schroit, A. J. (1990). Maintenance of lipid asymmetry in red blood cells and ghosts: effect of divalent cations and serum albumin on the transbilayer distribution of phosphatidylserine. Biochimica et Biophysica Acta 1025, 82–6.
Dluzewski, A. R., Rangachari, K., Wilson, R. J. M. & Gratzer, W. B. (1983). A cytoplasmic requirement of red cells for invasion by malarial parasites. Molecular and Biochemical Parasitology 9, 145–60.
Dluzewski, A. R., Ling, I. T., Rangachari, K., Bates, P. A. & Wilson, R. J. M. (1984). A simple method for isolating viable mature parasites of Plasmodium falciparum from cultures. Transactions of the Royal Society of Tropical Medicine and Hygiene 78, 622–4.
Flatman, P. W. & Lew, V. L. (1980). Magnesium buffering in intact human red blood cells measured using the ionophore A23187. Journal of Physiology 305, 1330.
Friedman, M. J. (1983). Control of malaria virulence by α1-acid glycoprotein (orosomucoid), an acute-phase inflammatory reactant. Proceedings of the National Academy of Sciences, USA 80, 5421–4.
Friedman, M. J., Blankenberg, T., Sensabaugh, G. & Tenforde, T. S. (1984). Recognition and invasion of human erythrocytes by malarial parasites: contribution of sialoglycoproteins to attachment and host specificity. Journal of Cell Biology 98, 1672–7.
Froman, G., Acevedo, F. & Hjertén, S. (1980). A molecular sieving method of preparing erythrocyte membranes. Preparative Biochemistry 10, 5967.
Gupta, C. M. & Mishra, G. C. (1981). Transbilayer phospholipid asymmetry in Plasmodium knowlesi-infected host cell membrane. Science 212, 1047–9.
Henseleit, U., Plasa, G. & Haest, C. (1990). Effects of divalent cations on lipid flip-flop in the human erythrocyte membrane. Biochimica et Biophysica Acta 1029, 127–35.
Joshi, P., Dutta, G. & Gupta, C. M. (1987). An intracellular simian malaria parasite (Plasmodium knowlesi) induces stage-dependent alterations in membrane phospholipid organization of its host cell membrane. The Biochemical Journal 246, 103–8.
Joshi, P. & Gupta, C. M. (1988). Abnormal membrane phospholipid organization in Plasmodium falciparum-infected human erythrocytes. British Journal of Haematology 68, 255–9.
Kaibuchi, K., Takai, Y. & Nishizuka, Y. (1981) Cooperative roles of various membrane phospholipids in the activation of calcium-activated, phospholipid-dependent protein kinase. Journal of biological Chemistry 256, 7146–9.
Laemmli, U. K. (1979). Cleavage of structural proteins during the assembly of bacteriophage T4. Nature, London 227, 680–5.
Lieber, M. L. & Steck, T. L. (1982). A description of the holes in human erythrocyte membrane ghosts. Journal of Biological Chemistry 257, 11651–9.
Lorand, L., Weismann, L. B., Epel, D. L., & Bruner-Lorand, J. (1976). Role of the intrinsic transglutaminase in the Ca2+-mediated crosslinking of erythrocyte proteins. Proceedings of the National Academy of Sciences, USA 73, 4479–81.
Maguire, P. A., Prudhomme, J. & Sherman, I. W. (1991). Alterations in erythrocyte membrane phospholipid organization due to intracellular growth of the human malaria parasite, Plasmodium falciparum. Parasitology 102, 179–86.
Maksymiw, R., Sui, S-F., Gaub, H. & Sackmann, E. (1987). Electrostatic coupling of spectrin dimers to phosphatidylserine containing lipid lamellae. Biochemistry 26, 2983–90.
Moll, G. N., Vial, H. J., Bevers, E. M., Ancolin, M. L., Roelofsen, B., Comfurius, P., Slotboom, A. J., Zwaal, R. F. A., Op Den Kamp, J. A. F. & Van Deenen, L. L. M. (1990). Phospholipid asymmetry in the plasma membrane of malaria infected erythrocytes. Biochemistry and Cell Biology 68, 579–85.
Murakami, T., Hatanaka, M. & Murachi, T. (1981). The cytosol of human erythrocytes contains a highly Ca2+-sensitive thiol protease (calpain I) and its specific inhibitor protein (calpastatin). Journal of Biochemistry 90, 1809–16.
Olson, J. A. & Kilejian, A. (1982). Involvement of spectrin and ATP in infection of resealed erythrocyte ghosts by the human malaria parasite Plasmodium falciparum. Journal of Cell Biology 95, 757–62.
Rangachari, K., Dluzewski, A. B., Wilson, R. J. M. & Gratzer, W. B. (1986). Control of malarial invasion by phosphorylation of the host cell membrane cytoskeleton. Nature, London 324, 364–5.
Schwartz, R. W., Olson, J. A., Raventos-Suarez, C., Yee, M., Heath, R. H., Lubin, B. & Nagel, R. L.(1987). Altered plasma membrane phospholipid organization in Plasmodium falciparum-infected human erythrocytes. Blood 69, 401–7.
Sherman, I. W. & Valdez, E. (1989). In vitro cytoadherence of Plasmodium falciparum-infected erythrocytes to melanoma cells: factors affecting adhesion. Parasitology 98, 359–69.
Thomas, P. G. & Verkleij, A. J. (1990). The dissimilar interactions of the calcium antagonist flunarizine with different phospholipid classes and molecular species: a differential scanning calorimetry study. Biochimica et Biophysica Acta 1030, 211–22.
Thomas, P. G., Zimmermann, A. G. & Verkleij, A. J. (1988). Prevention of calcium-induced membrane structural alterations in erythrocyte membranes by flunarizine. Biochimica et Biophysica Acta 946, 439–44.
Trager, W. & Jensen, J. B. (1976). Human malaria parasites in continuous culture. Science 193, 673–5.
Van Der Schaft, P. H., Beaumelle, B., Vial, H., Roelsofsen, B., Op Den Kamp, J. A. F. & Van Deenen, L. L. M. (1987). Phospholipid organization in monkey erythrocytes upon Plasmodium knowlesi infection. Biochimica et Biophysica Acta 901, 114.
Williamson, P., Alparin, L., Bateman, J., Choe, H-R. & Schlegel, B. A. (1985). Phospholipid asymmetry in human erythrocyte ghosts. Journal of Cellular Physiology 123, 209–14.
Zachowski, A., Fellmann, P., Hervé, P. & Devaux, P. F. (1987). Labelling of human erythrocyte membrane protein by photoactivable radioiodinated phosphatidylcholine and phosphatidylserine. A search for the aminophospholipid translocase. FEBS Letters 223, 315–20.
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