scholarly journals Local Hematocrit Fluctuation Induced by Malaria-Infected Red Blood Cells and Its Effect on Microflow

2018 ◽  
Vol 2018 ◽  
pp. 1-14
Author(s):  
Tong Wang ◽  
Zhongwen Xing
Keyword(s):  
Blood Flow ◽  
Plasmodium Falciparum ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Volume Fraction ◽  
Numerical Approach ◽  
Infected Rbcs ◽  
Infected Cells ◽  
Slow Moving ◽  
Cell Free Layer

We investigate numerically the microscale blood flow in which red blood cells (RBCs) are partially infected byPlasmodium falciparum, the malaria parasite. The infected RBCs are modeled as more rigid cells with less deformability than healthy ones. Our study illustrates that, in a 10 μm microvessel in low-hematocrit conditions (18% and 27%), thePlasmodium falciparum-infected red blood cells (Pf-IRBCs) and healthy ones first form a train of cells. Because of the slow moving of thePf-IRBCs, the local hematocrit (Hct) near thePf-IRBCs is then increased, to approximately40%or even higher values. This increase of the local hematocrit is temporary and is kept for a longer length of time because of the long RBC train formed in 27%-Hctcondition. Similar hematocrit elevation at the downstream region with 45%-Hctin the same 10 μm microvessel is also observed with the cells randomly located. In 20 μm microvessels with 45%-Hct, thePf-IRBCs slow down the velocity of the healthy red blood cells (HRBCs) around them and then locally elevate the volume fraction and result in the accumulation of the RBCs at the center of the vessels, thus leaving a thicker cell free layer (CFL) near the vessel wall than normal. Variation of wall shear stress (WSS) is caused by the fluctuation of localHctand the distance between the wall and the RBCs. Moreover, in high-hematocrit condition (45%), malaria-infected cells have a tendency to migrate to the edge of the aggregates which is due to the uninterrupted hydrodynamic interaction between the HRBCs andPf-IRBC. Our results suggest that the existence of Pf-IRBCs is a nonnegligible factor for the fluctuation of hematocrit and WSS and also contributes to the increase of CFL of pathological blood flow in microvessels. The numerical approach presented has the potential to be utilized to RBC disorders and other hematologic diseases.

scholarly journals Effect of Cytoplasmic Viscosity on Red Blood Cell Migration in Small Arteriole-level Confinements

2019 ◽  
Author(s):  
Amir Saadat ◽  
Christopher J. Guido ◽  
Eric S. G. Shaqfeh
Keyword(s):  
Blood Cell ◽  
Red Blood Cells ◽  
Red Blood Cell ◽  
Blood Cells ◽  
Large Scale ◽  
Volume Fraction ◽  
Free Layer ◽  
Channel Size ◽  
Viscosity Contrast ◽  
Cell Free Layer

The dynamics of red blood cells in small arterioles are important as these dynamics affect many physiological processes such as hemostasis and thrombosis. However, studying red blood cell flows via computer simulations is challenging due to the complex shapes and the non-trivial viscosity contrast of a red blood cell. To date, little progress has been made studying small arteriole flows (20-40μm) with a hematocrit (red blood cell volume fraction) of 10-20% and a physiological viscosity contrast. In this work, we present the results of large-scale simulations that show how the channel size, viscosity contrast of the red blood cells, and hematocrit affect cell distributions and the cell-free layer in these systems. We utilize a massively-parallel immersed boundary code coupled to a finite volume solver to capture the particle resolved physics. We show that channel size qualitatively changes how the cells distribute in the channel. Our results also indicate that at a hematocrit of 10% that the viscosity contrast is not negligible when calculating the cell free layer thickness. We explain this result by comparing lift and collision trajectories of cells at different viscosity contrasts.

scholarly journals Plasmodium falciparum-infected red blood cells depend on a functional glutathione de novo synthesis attributable to an enhanced loss of glutathione

2000 ◽  
Vol 346 (2) ◽  
pp. 545-552 ◽  
Author(s):  
Kai LÜERSEN ◽  
Rolf D. WALTER ◽  
Sylke MÜLLER
Keyword(s):  
Plasmodium Falciparum ◽  
Red Blood Cells ◽  
Blood Cells ◽  
De Novo ◽  
Specific Inhibitor ◽  
De Novo Synthesis ◽  
Glutamylcysteine Synthetase ◽  
Infected Rbcs ◽  
Erythrocytic Cycle ◽  
Gsh Metabolism

During the erythrocytic cycle, Plasmodium falciparum is highly dependent on an adequate thiol status for its survival. Glutathione reductase as well as de novo synthesis of GSH are responsible for the maintenance of the intracellular GSH level. The first and rate-limiting step of the synthetic pathway is catalysed by γ-glutamylcysteine synthetase (γ-GCS). Using L-buthionine-(S,R)-sulphoximine (BSO), a specific inhibitor of the γ-GCS, we show that the infection with P. falciparum causes drastic changes in the GSH metabolism of red blood cells (RBCs). Infected RBCs lose GSH at a rate 40-fold higher than non-infected RBCs. The de novo synthesis of the tripeptide was found to be essential for parasite survival. GSH depletion by BSO inhibits the development of P. falciparum with an IC50 of 73 μM. The effect of the drug is abolished by supplementation with GSH or GSH monoethyl ester. Our studies demonstrate that the plasmodicidal effect of the inhibitor BSO does not depend on its specificity towards its target enzyme in the parasite, but on the changed physiological needs for the metabolite GSH in the P. falciparum-infected RBCs. Therefore the depletion of GSH is proposed as a chemotherapeutic strategy for malaria, and γ-GCS is proposed as a potential drug target.

scholarly journals Stage-Dependent Topographical and Optical Properties of Plasmodium Falciparum-Infected Red Blood Cells

2021 ◽  
Author(s):  
Katharina Preißinger ◽  
Beáta Vértessy ◽  
István Kézsmárki ◽  
Miklós Kellermayer ◽  
Petra Molnár
Keyword(s):  
Plasmodium Falciparum ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Imaging Study ◽  
Close Correlation ◽  
Functional Changes ◽  
Force Microscopy ◽  
Atomic Force ◽  
Infected Rbcs ◽  
Bright Field Microscopy

Abstract Efficient malaria treatment is a major healthcare challenge. Addressing this challenge requires in-depth understanding of malaria parasite maturation during the intraerythrocytic cycle. Exploring the structural and functional changes of the parasite through the intraerythrocytic stages and their impact on red blood cells (RBCs) is a cornerstone of antimalarial drug development. In order to precisely trace such changes, we performed a thorough imaging study of RBCs infected by Plasmodium falciparum, by using atomic force microscopy (AFM) and total internal reflection fluorescence microscopy (TIRF) supplemented with bright field microscopy for stage assignment. This multifaceted imaging approach allows to reveal structure–function relations via correlations of the parasite maturation with morphological and fluorescence properties of the stages. We established diagnostic patterns characteristic to the parasite stages based on the topographical profile of infected RBCs, which show close correlation with their fluorescence (TIRF) map. Furthermore, we found that hemozoin crystals exhibit a strong optical contrast, possibly due to the quenching of fluorescence. The topographical and optical features provide a tool for locating the hemozoin crystals within the RBCs and following their growth.

scholarly journals Selective permeabilization of the host cell membrane of Plasmodium falciparum-infected red blood cells with streptolysin O and equinatoxin II

2007 ◽  
Vol 403 (1) ◽  
pp. 167-175 ◽  
Author(s):  
Katherine E. Jackson ◽  
Tobias Spielmann ◽  
Eric Hanssen ◽  
Akinola Adisa ◽  
Frances Separovic ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Cell Membrane ◽  
Red Blood Cells ◽  
Host Cell ◽  
Blood Cells ◽  
Parasitophorous Vacuole ◽  
Host Cell Membrane ◽  
Streptolysin O ◽  
Infected Rbcs ◽  
Equinatoxin Ii

Plasmodium falciparum develops within the mature RBCs (red blood cells) of its human host in a PV (parasitophorous vacuole) that separates the host cell cytoplasm from the parasite surface. The pore-forming toxin, SLO (streptolysin O), binds to cholesterol-containing membranes and can be used to selectively permeabilize the host cell membrane while leaving the PV membrane intact. We found that in mixtures of infected and uninfected RBCs, SLO preferentially lyses uninfected RBCs rather than infected RBCs, presumably because of differences in cholesterol content of the limiting membrane. This provides a means of generating pure preparations of viable ring stage infected RBCs. As an alternative permeabilizing agent we have characterized EqtII (equinatoxin II), a eukaryotic pore-forming toxin that binds preferentially to sphingomyelin-containing membranes. EqtII lyses the limiting membrane of infected and uninfected RBCs with similar efficiency but does not disrupt the PV membrane. It generates pores of up to 100 nm, which allow entry of antibodies for immunofluorescence and immunogold labelling. The present study provides novel tools for the analysis of this important human pathogen and highlights differences between Plasmodium-infected and uninfected RBCs.

scholarly journals Functional alteration of red blood cells by a megadalton protein of Plasmodium falciparum

Blood ◽  
2009 ◽  
Vol 113 (4) ◽  
pp. 919-928 ◽  
Author(s):  
Fiona K. Glenister ◽  
Kate M. Fernandez ◽  
Lev M. Kats ◽  
Eric Hanssen ◽  
Narla Mohandas ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Membrane Skeleton ◽  
Membrane Structures ◽  
Rbc Membrane ◽  
Infected Rbcs ◽  
Membrane Rigidity ◽  
Transgenic Parasites ◽  
Normal Adhesion

AbstractProteins exported from Plasmodium falciparum parasites into red blood cells (RBCs) interact with the membrane skeleton and contribute to the pathogenesis of malaria. Specifically, exported proteins increase RBC membrane rigidity, decrease deformability, and increase adhesiveness, culminating in intravascular sequestration of infected RBCs (iRBCs). Pf332 is the largest (>1 MDa) known malaria protein exported to the RBC membrane, but its function has not previously been determined. To determine the role of Pf332 in iRBCs, we have engineered and analyzed transgenic parasites with Pf332 either deleted or truncated. Compared with RBCs infected with wild-type parasites, mutants lacking Pf332 were more rigid, were significantly less adhesive to CD36, and showed decreased expression of the major cytoadherence ligand, PfEMP1, on the iRBC surface. These abnormalities were associated with dramatic morphologic changes in Maurer clefts (MCs), which are membrane structures that transport malaria proteins to the RBC membrane. In contrast, RBCs infected with parasites expressing truncated forms of Pf332, although still hyperrigid, showed a normal adhesion profile and morphologically normal MCs. Our results suggest that Pf332 both modulates the level of increased RBC rigidity induced by P falciparum and plays a significant role in adhesion by assisting transport of PfEMP1 to the iRBC surface.

Ultrastructural observations on the in vitro cytoadherence of Plasmodium falciparum infected red blood cells

1990 ◽  
Vol 48 (3) ◽  
pp. 914-915
Author(s):  
D.J.P. Ferguson ◽  
A.R. Berendt ◽  
J. Tansey ◽  
K. Marsh ◽  
C.I. Newbold
Keyword(s):  
Plasmodium Falciparum ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Umbilical Vein ◽  
Cell Types ◽  
Amelanotic Melanoma ◽  
Cytoplasmic Process ◽  
Umbilical Vein Endothelial Cells

In human malaria, the most serious clinical manifestation is cerebral malaria (CM) due to infection with Plasmodium falciparum. The pathology of CM is thought to relate to the fact that red blood cells containing mature forms of the parasite (PRBC) cytoadhere or sequester to post capillary venules of various tissues including the brain. This in vivo phenomenon has been studied in vitro by examining the cytoadherence of PRBCs to various cell types and purified proteins. To date, three Ijiost receptor molecules have been identified; CD36, ICAM-1 and thrombospondin. The specific changes in the PRBC membrane which mediate cytoadherence are less well understood, but they include the sub-membranous deposition of electron-dense material resulting in surface deformations called knobs. Knobs were thought to be essential for cytoadherence, lput recent work has shown that certain knob-negative (K-) lines can cytoadhere. In the present study, we have used electron microscopy to re-examine the interactions between K+ PRBCs and both C32 amelanotic melanoma cells and human umbilical vein endothelial cells (HUVEC).We confirm previous data demonstrating that C32 cells possess numerous microvilli which adhere to the PRBC, mainly via the knobs (Fig. 1). In contrast, the HUVEC were relatively smooth and the PRBCs appeared partially flattened onto the cell surface (Fig. 2). Furthermore, many of the PRBCs exhibited an invagination of the limiting membrane in the attachment zone, often containing a cytoplasmic process from the endothelial cell (Fig. 2).

scholarly journals Mathematical Models for Some Aspects of Blood Microcirculation

Symmetry ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1020
Author(s):  
Angiolo Farina ◽  
Antonio Fasano ◽  
Fabio Rosso
Keyword(s):  
Blood Flow ◽  
Mathematical Models ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Blood Rheology ◽  
Small Class ◽  
Small Vessels ◽  
Blood Microcirculation ◽  
Peculiar Behavior

Blood rheology is a challenging subject owing to the fact that blood is a mixture of a fluid (plasma) and of cells, among which red blood cells make about 50% of the total volume. It is precisely this circumstance that originates the peculiar behavior of blood flow in small vessels (i.e., roughly speaking, vessel with a diameter less than half a millimeter). In this class we find arteriolas, venules, and capillaries. The phenomena taking place in microcirculation are very important in supporting life. Everybody knows the importance of blood filtration in kidneys, but other phenomena, of not less importance, are known only to a small class of physicians. Overviewing such subjects reveals the fascinating complexity of microcirculation.

scholarly journals Emergent cell-free layer asymmetry and biased haematocrit partition in a biomimetic vascular network of successive bifurcations

Soft Matter ◽  
2021 ◽  
Author(s):  
Qi Zhou ◽  
Joana Fidalgo ◽  
Miguel Bernabeu ◽  
Mónica S.N. Oliveira ◽  
Timm Krüger
Keyword(s):  
Red Blood Cells ◽  
Human Body ◽  
Blood Cells ◽  
Soft Matter ◽  
Vascular Network ◽  
Free Layer ◽  
Cell Free Layer

Blood is a vital soft matter, and its normal circulation in the human body relies on the distribution of red blood cells (RBCs) at successive bifurcations. Understanding how RBCs are...

Endothelin-1 production by a microvascular endothelial cell line treated with Plasmodium falciparum parasitized red blood cells

2002 ◽  
Vol 103 (s2002) ◽  
pp. 464S-466S ◽  
Author(s):  
Nicoletta BASILICO ◽  
Livianna SPECIALE ◽  
Silvia PARAPINI ◽  
Pasquale FERRANTE ◽  
Donatella TARAMELLI
Keyword(s):  
Plasmodium Falciparum ◽  
Endothelial Cell ◽  
Red Blood Cells ◽  
Cell Line ◽  
Blood Cells ◽  
Microvascular Endothelial Cell ◽  
Microvascular Endothelium ◽  
Endothelial Cell Line ◽  
Endothelin 1 ◽  
Microvascular Endothelial

In this study, we investigated the production of endothelin 1 (ET-1) by a human microvascular endothelial cell line, HMEC-1, co-cultured with Plasmodium falciparum-parasitized red blood cells (pRBCs). The results indicate that hypoxia increased the basal level of ET-1 production by HMEC-1 cells after 24 or 48h of treatment. However, the co-incubation of HMEC-1 cells with pRBCs, but not with uninfected RBCs, induced a dose-dependent decrease of both constitutive and hypoxia-induced ET-1 production. The inhibition was not due to a decrease in cell viability, as lactate dehydrogenase release remained constant. These results indicate that pRBCs are able to interfere with both the constitutive and stimulated ET-1 release from the microvascular endothelium, thus inducing local modifications of the vascular tone and of the inflammatory response. This could be of relevance in the pathogenesis of the most severe forms of P. falciparum infections, such as cerebral malaria or malaria during pregnancy.

Multiscale Modeling of Flow Induced Thrombogenicity Using Dissipative Particle Dynamics and Molecular Dynamics

2013 ◽  
Author(s):  
Danny Bluestein ◽  
João S. Soares ◽  
Peng Zhang ◽  
Chao Gao ◽  
Seetha Pothapragada ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Blood Flow ◽  
Red Blood Cells ◽  
Platelet Activation ◽  
Blood Cells ◽  
Dissipative Particle Dynamics ◽  
Particle Dynamics ◽  
Coagulation Cascade ◽  
Shear Stresses ◽  
Activated Platelets

The coagulation cascade of blood may be initiated by flow induced platelet activation, which prompts clot formation in prosthetic cardiovascular devices and arterial disease processes. While platelet activation may be induced by biochemical agonists, shear stresses arising from pathological flow patterns enhance the propensity of platelets to activate and initiate the intrinsic pathway of coagulation, leading to thrombosis. Upon activation platelets undergo complex biochemical and morphological changes: organelles are centralized, membrane glycoproteins undergo conformational changes, and adhesive pseudopods are extended. Activated platelets polymerize fibrinogen into a fibrin network that enmeshes red blood cells. Activated platelets also cross-talk and aggregate to form thrombi. Current numerical simulations to model this complex process mostly treat blood as a continuum and solve the Navier-Stokes equations governing blood flow, coupled with diffusion-convection-reaction equations. It requires various complex constitutive relations or simplifying assumptions, and is limited to μm level scales. However, molecular mechanisms governing platelet shape change upon activation and their effect on rheological properties can be in the nm level scales. To address this challenge, a multiscale approach which departs from continuum approaches, may offer an effective means to bridge the gap between macroscopic flow and cellular scales. Molecular dynamics (MD) and dissipative particle dynamics (DPD) methods have been employed in recent years to simulate complex processes at the molecular scales, and various viscous fluids at low-to-high Reynolds numbers at mesoscopic scales. Such particle methods possess important properties at the mesoscopic scale: complex fluids with heterogeneous particles can be modeled, allowing the simulation of processes which are otherwise very difficult to solve by continuum approaches. It is becoming a powerful tool for simulating complex blood flow, red blood cells interactions, and platelet-mediated thrombosis involving platelet activation, aggregation, and adhesion.

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