Plasmodium falciparum: Role of Activated Blood Monocytes in Erythrocyte Membrane Damage and Red Cell Loss during Malaria

Abstract During intraerythrocytic growth of Plasmodium falciparum, several parasite proteins are transported from the parasite to the erythrocyte membrane, where they bind to membrane skeletal proteins. Mature-parasite-infected erythrocyte surface antigen (MESA) has previously been shown to associate with host erythrocyte membrane skeletal protein 4.1. Using a spontaneous mutant of P falciparum that has lost the ability to synthesize MESA and 4.1-deficient erythrocytes, we examined growth of MESA(+) and MESA(-) parasites in normal and 4.1-deficient erythrocytes. Viability of MESA(+) parasites was reduced in 4.1-deficient erythrocytes as compared with that for normal erythrocytes, but MESA(-) parasites grew equally well in 4.1-deficient and normal erythrocytes. Cytoadherence of MESA(+)- and MESA (-)-parasitized normal and 4.1-deficient erythrocytes to C32 melanoma cells was similar, indicating that neither protein 4.1 nor MESA plays a major role in cytoadherence of infected erythrocytes. Localization of MESA in normal and 4.1-deficient erythrocytes was examined by confocal microscopy. MESA was diffusely distributed in the cytosol of 4.1-deficient erythrocytes but was membrane-associated in normal erythrocytes. These findings suggest that MESA binding to protein 4.1 plays a major role in intraerythrocytic parasite viability.

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Allelic Diversity of the Plasmodium falciparum Erythrocyte Membrane Protein 1 Entails Variant-Specific Red Cell Surface Epitopes

PLoS ONE ◽

10.1371/journal.pone.0016544 ◽

2011 ◽

Vol 6 (1) ◽

pp. e16544 ◽

Cited By ~ 33

Author(s):

Inès Vigan-Womas ◽

Micheline Guillotte ◽

Alexandre Juillerat ◽

Cindy Vallieres ◽

Anita Lewit-Bentley ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Membrane Protein ◽

Cell Surface ◽

Erythrocyte Membrane ◽

Allelic Diversity ◽

Red Cell ◽

Erythrocyte Membrane Protein ◽

Falciparum Erythrocyte Membrane Protein

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Receptors on red cells for Plasmodium falciparum and their interaction with merozoites

Philosophical Transactions of the Royal Society of London Series B Biological Sciences ◽

10.1098/rstb.1984.0119 ◽

1984 ◽

Vol 307 (1131) ◽

pp. 189-200 ◽

Cited By ~ 34

Keyword(s):

Plasmodium Falciparum ◽

Hydrophobic Interactions ◽

Membrane Lipid ◽

Red Cells ◽

Red Cell ◽

Naturally Occurring ◽

Electrostatic And Hydrophobic Interactions ◽

Wheatgerm Agglutinin ◽

Human Red Cells

The red cell sialoglycoproteins (glycophorins, The red cell sialoglycoproteins (glycophorins, α(A), δ(B) and β and γ(C)) play a crucial role in the invasion of human red cells by merozoites of Plasmodium falciparum . Red cells deficient in any of the glycophorins, including β (also known as glycoconnectin), resist infection by this parasite to varying degrees. These cells and other naturally occurring well-characterized glycophorin variants provide extremely powerful tools to dissect the role of these molecules in invasion. The binding of merozoites to human red cells appears analogous to the binding of wheatgerm agglutinin to sialoglycoconjugates. In both systems O- and N-linked oligosaccharides may be involved. Membrane lipid has not been implicated as a receptor for merozoites, but may instead non-specifically modify binding, as may electrostatic and hydrophobic interactions. The results of data using monoclonal antibodies and lectins, although possibly helpful in identifying specific determinants, must be interpreted with caution. Overall the data suggest that the red cell receptors for all strains of P. falciparum tested to date are located on the glycophorins. Accordingly these putative receptors have been used to affinity-purify complementary parasite components which may yet prove to be of protective immunological significance in a vaccine.

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Flow cytometric assessment of oxidant stress in age-fractionated thalassaemic trait erythrocytes and its relationship to in vitro growth of Plasmodium falciparum

Parasitology ◽

10.1017/s0031182097001911 ◽

1998 ◽

Vol 116 (1) ◽

pp. 1-6 ◽

Cited By ~ 15

Author(s):

A. C. SENOK ◽

K. LI ◽

E. A. S. NELSON ◽

M. ARUMANAYAGAM ◽

C. K. LI

Keyword(s):

Plasmodium Falciparum ◽

Oxidant Stress ◽

Inverse Correlation ◽

Malarial Parasite ◽

Red Cell ◽

Flow Cytometric ◽

Age Related ◽

Cell Age

The role of oxidant stress in mediating the protection against malaria in thalassaemic red blood cells (RBC) has been hypothesized. In this study we have assessed the relationship between oxidant stress, red cell age and malarial parasite activity in thalassaemic RBC. Using a flow cytometric method to assess lipid peroxidation, we have shown that the age-related increase in sensitivity to oxidative stress previously demonstrated in normal RBC also occurs in thalassaemic RBC. Invasion and growth of Plasmodium falciparum was also shown to deteriorate with increasing RBC age. This effect was more pronounced in thalassaemic RBC with associated schizont maturation arrest and abnormal parasite morphology. In addition, there was a slight but consistent inverse correlation between sensitivity to oxidant stress and parasite activity (R=−0·43; P=0·03 for normal RBC and R=−0·42; P=0·01 for thalassaemic RBC). Our findings indicate an association between red cell age, oxidant stress and P. falciparum growth, providing further support for the role of oxidant stress in mediating the protective effect against malaria in thalassaemic RBC.

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Role of the Plasmodium falciparum mature-parasite-infected erythrocyte surface antigen (MESA/PfEMP-2) in malarial infection of erythrocytes

Blood ◽

10.1182/blood.v86.8.3196.bloodjournal8683196 ◽

1995 ◽

Vol 86 (8) ◽

pp. 3196-3204

Author(s):

C Magowan ◽

RL Coppel ◽

AO Lau ◽

MM Moronne ◽

G Tchernia ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Erythrocyte Membrane ◽

Surface Antigen ◽

Infected Erythrocyte ◽

Spontaneous Mutant ◽

Protein 4.1 ◽

Erythrocyte Surface ◽

Skeletal Protein ◽

Parasite Viability

During intraerythrocytic growth of Plasmodium falciparum, several parasite proteins are transported from the parasite to the erythrocyte membrane, where they bind to membrane skeletal proteins. Mature-parasite-infected erythrocyte surface antigen (MESA) has previously been shown to associate with host erythrocyte membrane skeletal protein 4.1. Using a spontaneous mutant of P falciparum that has lost the ability to synthesize MESA and 4.1-deficient erythrocytes, we examined growth of MESA(+) and MESA(-) parasites in normal and 4.1-deficient erythrocytes. Viability of MESA(+) parasites was reduced in 4.1-deficient erythrocytes as compared with that for normal erythrocytes, but MESA(-) parasites grew equally well in 4.1-deficient and normal erythrocytes. Cytoadherence of MESA(+)- and MESA (-)-parasitized normal and 4.1-deficient erythrocytes to C32 melanoma cells was similar, indicating that neither protein 4.1 nor MESA plays a major role in cytoadherence of infected erythrocytes. Localization of MESA in normal and 4.1-deficient erythrocytes was examined by confocal microscopy. MESA was diffusely distributed in the cytosol of 4.1-deficient erythrocytes but was membrane-associated in normal erythrocytes. These findings suggest that MESA binding to protein 4.1 plays a major role in intraerythrocytic parasite viability.

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Leucocytes and Thrombosis

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649101 ◽

1973 ◽

Vol 30 (01) ◽

pp. 047-061 ◽

Cited By ~ 1

Author(s):

D.C Banks ◽

J.R.A Mitchell

Keyword(s):

Cell Adhesion ◽

Whole Blood ◽

Divalent Cations ◽

Potassium Cyanide ◽

Cell Loss ◽

White Cell ◽

Red Cells ◽

Red Cell ◽

Sulphydryl Groups

SummaryThe rate of white cell loss from heparinised whole blood in a rotating glass flask has been used to study leucocyte behaviour.Leucocyte loss requires divalent cations and magnesium is more active than calcium. Sulphydryl blockers and potassium cyanide inhibit white cell loss, showing that sulphydryl groups and a glycolytic pathway play a part in leucocyte adhesion.White cell loss from plasma rotated in a flask is negligible, but is markedly increased by adding red cells, red cell sonicates or ADP.The role of platelets and of substances which affect platelet behaviour in white cell adhesion is discussed.

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The role of PfEMP1 as targets of naturally acquired immunity to childhood malaria: prospects for a vaccine

Parasitology ◽

10.1017/s0031182015001274 ◽

2016 ◽

Vol 143 (2) ◽

pp. 171-186 ◽

Cited By ~ 29

Author(s):

PETER C. BULL ◽

ABDIRAHMAN I. ABDI

Keyword(s):

Plasmodium Falciparum ◽

Membrane Protein ◽

Severe Malaria ◽

Erythrocyte Membrane ◽

Molecular Diversity ◽

Acquired Immunity ◽

Recent Developments ◽

Childhood Malaria ◽

Lines Of Evidence

SUMMARYThePlasmodium falciparumerythrocyte membrane protein 1 antigens that are inserted onto the surface ofP. falciparuminfected erythrocytes play a key role both in the pathology of severe malaria and as targets of naturally acquired immunity. They might be considered unlikely vaccine targets because they are extremely diverse. However, several lines of evidence suggest that underneath this molecular diversity there are a restricted set of epitopes which may act as effective targets for a vaccine against severe malaria. Here we review some of the recent developments in this area of research, focusing on work that has assessed the potential of these molecules as possible vaccine targets.

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The orientation of sickle hemoglobin fibers within fascicles

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100104066 ◽

1988 ◽

Vol 46 ◽

pp. 400-401

Author(s):

Christopher A. Miller ◽

Bridget Carragher ◽

William A. McDade ◽

Robert Josephs

Keyword(s):

Sickle Cell ◽

Sickle Cell Anemia ◽

Relative Orientation ◽

Unit Cell ◽

Red Cell ◽

High Ph ◽

Sickle Hemoglobin ◽

Polar Crystal ◽

Helical Configuration

Highly ordered bundles of deoxyhemoglobin S (HbS) fibers, termed fascicles, are intermediates in the high pH crystallization pathway of HbS. These fibers consist of 7 Wishner-Love double strands in a helical configuration. Since each double strand has a polarity, the odd number of double strands in the fiber imparts a net polarity to the structure. HbS crystals have a unit cell containing two double strands, one of each polarity, resulting in a net polarity of zero. Therefore a rearrangement of the double strands must occur to form a non-polar crystal from the polar fibers. To determine the role of fascicles as an intermediate in the crystallization pathway it is important to understand the relative orientation of fibers within fascicles. Furthermore, an understanding of fascicle structure may have implications for the design of potential sickling inhibitors, since it is bundles of fibers which cause the red cell distortion responsible for the vaso-occlusive complications characteristic of sickle cell anemia.

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