Erythrocyte Membrane Deformability Research Articles

Alterations in plasma and erythrocyte membrane fatty acid composition following exposure to toxic copper level affect membrane deformability and fluidity in female wistar rats

BackgroundDeformability and fluidity function of the red blood cell membrane are properties defined by the lipid composition. Toxic copper level induces membrane lipid peroxidation which could cause membrane instability. This study therefore investigated the effect of exposure to toxic copper level for 30 days on red blood cell membrane deformability and fluidity in female Wistar rats. MethodsTwelve (12) female Wistar rats (160 ± 10 g) were randomly grouped (n = 6) into control (given 0.1 ml distilled water p.o.) and copper-toxic (100 mg/kg Copper Sulphate, p.o.), and treated for 30 days. Plasma obtained and RBC membrane prepared from blood collected over EDTA post-treatment were assayed for total cholesterol (TC), phospholipids and fatty acid profile using spectrophotometry and Gas chromatography while heparinized blood was subjected to fragility test. Data were analyzed using student T-test for statistical significance at p < 0.05. Results and conclusionPlasma TC increased by 4.33% while RBC membrane TC decreased by 20.32% in copper-toxic group compared to control. Compared to control, excess copper significantly increased membrane phospholipids level (0.72 ± 0.01 vs 0.59 ± 0.04 mg/dL) but reduced membrane cholesterol/phospholipid ratio (46.61 ± 4.72 vs 72.66 ± 6.47) and stability (by 23.53%). Number of cis- and saturated fatty acids increased in copper-treated plasma and RBC membrane compared to control. Exposure to toxic copper level alters erythrocyte membrane fluidity and deformability by disrupting membrane lipid composition, saturation, bond configuration in phospholipids and permeability.

Deformability Of Erythrocytes And Microcirculation In Old Patients With Hypoxia Of Various Genesis

Age-related changes in the deformability of erythrocyte membranes against the background of heart and respiratory failure exacerbate disorders of the blood supply to tissues and organs at the microcirculatory level, which is an important factor in worsening the prognosis of the disease, especially in people over 60 years of age. The purpose of the work is to investigate the patterns of changes in the deformability of erythrocyte membranes against the background of heart and respiratory failure in older people. In older patients against the background of COPD and CHF, a decrease in the deformability of erythrocyte membranes and associated microcirculation disorders against the background of hypoxia are detected. Age-related physiological changes in the morpho-functional state of erythrocyte membranes and changes in the deformability of their membranes against the background of somatic pathology (heart, respiratory failure, fever) lead to a syndrome of mutual weighting, exacerbate disorders of the blood supply to tissues and organs at the microcirculatory level, which is an important factor in worsening the prognosis diseases, especially in people over 65 years of age.

Role of Plasma Membrane at Dielectric Relaxations and Intermembrane Interaction in Human Erythrocytes.

Dielectric relaxations at 1.4 MHz (βsp) and 9 MHz (γ1sp) on the erythrocyte spectrin network were studied by dielectric spectroscopy using dense suspensions of erythrocytes and erythrocyte ghost membranes, subjected to extraction with up to 0.2% volume Triton-X-100. The step-wise extraction of up to 60% of membrane lipids preserved γ1sp and gradually removed βsp-relaxation. On increasing the concentration up to 100 mM of NaCl at either side of erythrocyte plasma membranes, the βsp-relaxation was linearly enhanced, while the strength of γ1sp-relaxation remained unchanged. In media with NaCl between 100 and 150 mM βsp-relaxation became slightly inhibited, while γ1sp-relaxation almost disappeared, possibly due to the decreased electrostatic repulsion allowing erythrocytes to come into closer contact. When these media contained, at concentrations 10-30 mg/mL dextran (MW 7 kDa), polyethylene glycol or polyvinylpyrrolidone (40 kDa), or albumin or homologous plasma with equivalent concentration of albumin, the γ1sp-relaxation was about tenfold enhanced, while βsp-relaxation was strengthened or preserved. The results suggest the Maxwell-Vagner accumulation of ions on the lipid bilayer as an energy source for βsp-relaxation. While βsp-relaxation appears sensitive to erythrocyte membrane deformability, γ1sp-relaxation could be a sensitive marker for the inter-membrane interactions between erythrocytes.

Segmental flexibility of spectrin reflects erythrocyte membrane deformability

The frequency-dependent contribution of spectrin, the main cytoskeletal protein of red blood cell (RBC) membrane, to the complex admittance and capacitance of suspended RBCs have revealed two dielectric relaxations, βsp (1.4 MHz) and γ1sp (7 MHz). The strength of these relaxations was related to the ability of RBC membrane to deform. In this study the two relaxations were inhibited by N-ethylmaleimide (up to 5 mM), known to impair the RBC deformability, and the degree of inhibition, i.e., the number of accessible SH-groups on spectrin, depended on the deformation of RBC membrane. Dithiothreitol (up to 5 mM), which does not affect RBC deformability, did not affect the above dielectric relaxations in line with the absence of S-S groups on spectrin. Phenylhydrazine (up to 3 mM) and hydrogen hydroperoxide (up to 450 μM) are known to denature the haemoglobin of RBCs producing nanoparticles (globins) that bind to spectrin turning the RBC membrane rigid. At the same concentrations they were shown to inhibit progressively the two relaxations on spectrin. The results are in line with the involvement of some globin-sized segments of spectrin in the dielectric activity of spectrin and in the ability of RBC plasma membrane to deform.

Rheological parameters as prognostic factors in blood loss

The aim of the work was to study the rheological status in experimental blood loss of varying severity. The experiments were carried out on out bred male rats. De-pending on the severity of blood loss, the animals were divided into subgroups. In each subgroup, the erythrocyte aggregation index, erythrocyte membrane deformability index, and blood plasma viscosity were measured. As a result of statistical data processing, it was found that in case of blood loss of any severity, erythrocyte aggregation plays a leading role, followed by the blood viscosity parameter, and changes in membrane deformability are significant only in the decompensatory phase. Thus, it is once again emphasized that with blood loss, the presence of a persistent, starting from the first stage, changes in the rheological status, which mainly depends on the profile of erythrocyte aggregation. These experimental data, coupled with changes in the viscosity and membrane deformability of erythrocytes in the later stages of blood loss, lead to the idea of a careful use of the mass of erythrocytes for the treatment of critical conditions caused by blood loss. Continuation of experimental studies and translation of their findings into clinical medicine will most likely im-prove treatment tactics and increase its effectiveness in the treatment of patients with hemorrhagic shock.

Changes in the Deformability and Resistance of Erythrocyte Membranes under the Action of Gamma-Aminobutyric Acid Derivatives in the Offspring of Rats with Experimental Preeclampsia

INTRODUCTION: Preeclampsia is a severe complication of pregnancy associated with the negative consequences for the mother and child. Such complications can be a reduction in the resistance of erythrocyte membranes to damaging agents and alteration of rheological properties of the blood in offspring. Promising compounds for the correction of these negative consequences of preeclampsia are gamma-aminobutyric acid (GABA) derivatives, which showed membraneprotective, antioxidant, and antihypoxic effects in previous studies.&#x0D; AIM: To evaluate the effect of GABA derivatives Succicard (4-phenylpiracetam and ethane-1,2-dicarboxylic acid, 2:1), Salifen (4-amino-3-phenylbutanoic acid and 2-hydroxybenzoic acid, 2:1), and Phenibut (aminophenylbutyric acid) on the deformability and resistance of erythrocyte membranes in 8- and 14-month-old offspring of rats with experimental preeclampsia (EP).&#x0D; MATERIALS AND METHODS: The study involved offspring (male and female) of white non-inbred female rats with a normal pregnancy and EP that was modeled by replacement of drinking water with a 1.8% sodium chloride solution during gestation (121 days). For 30 days (from day 40 to day 70 of life), pup rats intragastrically received Succicard (22 mg/kg), Salifen (7.5 mg/kg), and Phenibut (25 mg/kg), along with a comparison drug Pantogam (calcium gopantenate) (50 mg/day) once a day. The offspring of the positive and negative control groups were injected with distilled water in a similar mode. In offspring aged 8 and 14 months, the resistance of erythrocyte membranes to the action of hydrochloric acid and their deformability were determined.&#x0D; RESULTS: In 8-month-old male offspring of rats with EP, a shorter time of achievement of half the maximal amplitude of erythrogram was noted in acid hemolysis relative to the positive control group, and the erythrocyte elongation index was reduced. Relative to the negative control group, Succicard, Salifen, Phenibut, and Pantogam promoted the prolongation of hemolysis and the erythrocyte elongation index in 8-month-old male rats in the experimental groups. In 14-month-old male and female rats of different ages, no statistically significant differences were found between the groups.&#x0D; CONCLUSION: Changes in the stiffness and strength of erythrocyte membranes were noted only in male offspring of rats with EP. Succicard, Salifen, Phenibut, and Pantogam produced membrane-protective effects on the erythrocytes of 8-month-old male rats of the experimental groups.

Supervised Cycling Training Improves Erythrocyte Rheology in Individuals With Peripheral Arterial Disease.

Peripheral arterial disease (PAD) results in insufficient flow to lower extremities. Aerobic exercise provides health benefits for individuals with PAD, but basic science behind it is still debated. Twenty-one PAD patients aged about 70 years with female/male as 7/14 were recruited. Among them, 11 were randomized to have supervised cycling training (SCT) and 10 to receive general healthcare (GHC) as controls. SCT participants completed 36 sessions of SCT at the first ventilation threshold within 12 weeks and the controls received GHC for 12 weeks. Ankle-brachial index (ABI), 6-min walk test (6MWT), peak oxygen consumption (O2peak), minute ventilation (E), minute carbon dioxide production (CO2), erythrocyte rheology, including the maximal elongation index (EImax) and shear stress at 50% of maximal elongation (SS1/2), and the Short Form-36 (SF-36) questionnaire for quality of life (QoL) were assessed before and 12 weeks after initial visit. SCT significantly decreased the SS1/2 as well as SS1/2 to EImax ratio (SS1/2/EImax) and increased the erythrocyte osmolality in the hypertonic region as well as the area under EI-osmolality curve. The supervised exercise-induced improvement of erythrocyte deformability could contribute to the increased peripheral tissue O2 delivery and was possibly related with increased O2peak. The physiological benefit was associated with significantly increased ABI, 6-min walking distance, cardiorespiratory fitness, and SF-36 score. However, no significant changes in aerobic capacity and erythrocyte rheological properties were observed after 12-week of GHC. In conclusion, SCT improves aerobic capacity by enhancing erythrocyte membrane deformability and consequently promotes QoL in PAD patients.

&lt;p&gt;&lt;strong&gt;Compositional alterations in erythrocyte membranes in Type II diabetes&lt;/strong&gt;&lt;/p&gt;

Loss of erythrocyte membrane deformability is one of the most crucial factors in developing complications associated with Type II diabetes. The observed loss of erythrocyte membrane deformability could be related to structural changes in the membrane. In this context, here, we have made an attempt at gaining a better insight (quantitative as well as qualitative) into the protein and lipid contents in erythrocyte membranes and their interrelationships in Type II diabetes. Age matched control (n=12) and Type II diabetic subjects (n=22) were selected for this study. Morphological characteristics were studied by atomic force microscopy (AFM). AFM study confirmed remarkable alterations in morphology of the diabetic erythrocytes. In diabetic erythrocytes following changes were noted: (i) Significant increase in membrane as well as cytosolic proteins with a marginal increase in phospholipids content; (ii) The membrane total lipids:protein, phospholipids:protein, cholesterol:protein and phospholipids:cholesterol (mole:mole) ratios decreased significantly; (iii). A reproducible decrease in docosahexaenoic acid (DHA) and Omega-3 index with increase in Omega-6:Omega-3 ratio in membrane fatty acids; and (iv) The SDS-PAGE analysis indicated that all membrane proteins increased in almost equal proportion leading to increased membrane protein content. The observed compositional and stochiometric changes in lipids, proteins and their ratios may underlie morphological alterations and loss of deformability.

Hemolysis in the Spleen Drives Erythrocyte Turnover

Erythrocytes circulate for an average of 120 days before they are removed from the circulation. Various processes and factors have been identified that may contribute to degradation of senescent erythrocytes, but this complex process is still not completely understood. Accumulation of removal signals such as phosphatidylserine exposure, changes in CD47 expression and oxidation of proteins and lipids that render them susceptible to complement deposition, may contribute to recognition and degradation by red pulp macrophages (RPM) of the spleen. However, many questions remain on the exact mechanisms that determine the fate of aged erythrocytes. This is well exemplified in a mouse study in which physiologically aged erythrocytes were found to undergo phagocytosis by RPM in vivo but not in vitro. This finding suggested that the splenic architecture may play an important role in facilitating erythrocyte turnover. Loss of membrane deformability may lead to the initial trapping of aged or damaged erythrocytes in the spleen, an event that precedes their degradation by macrophages. Loss of deformability can explain why certain genetic diseases that affect erythrocyte membrane deformability, such as is the case in sickle cell disease and spherocytosis, result in trapping in the spleen, giving rise to anaemia. Next to loss of deformability, activation of adhesion molecules, such as Lu/BCAM and CD44, specifically on aged erythrocytes has been proposed to contribute to retention of erythrocytes within the spleen, leading to their turnover. In this study we provide evidence that the splenic environment is of key importance in facilitating erythrocyte turnover through induction of hemolysis. Upon isolating human spleen RPM we noted that only a small proportion of the macrophages were in the process of phagocytosing intact erythrocytes. Based on a range of variables, including the number of erythrocytes that are cleared daily, the number of RPM present in the spleen, the degradation rate of erythrocytes as well as differential contribution of spleen and liver to erythrocyte turnover, conservative estimates approximate that at least a 30-fold fewer erythrophagocytic events are observed in RPM than anticipated. Detailed characterization of erythrocyte and macrophage subpopulations from human spleen tissue led to the identification of a large population of erythrocytes that are devoid of hemoglobin, so-called erythrocyte ghosts. By in vivo imaging of the spleen and transfusion experiments we further confirmed that senescent erythrocytes that are retained in the spleen are subject to hemolysis, thereby forming erythrocyte ghosts. Of note, we found that the levels of haptoglobin and hemopexin, two plasma proteins that are involved in scavenging of haemoglobin and heme, respectively, correlate well with the rate of hemolysis that was observed in the spleen. Additionally, we show that the erythrocyte adhesion molecules which are specifically activated on aged erythrocytes, Lu/BCAM and CD44, cause senescent erythrocytes to interact with the extracellular matrix of the spleen. This adhesion molecule-driven retention of senescent erythrocytes, under low shear conditions, was found to result in steady shrinkage of the erythrocytes and ultimately resulted in hemolysis and ghost formation. In contrast to intact senescent erythrocytes, the remnant erythrocyte ghosts were found to be immediately recognized and rapidly degraded (1-3 hours) by RPM, thereby explaining the lack of phagocytosis of intact erythrocytes in the spleen. Together, these data identify hemolysis and ghost formation as key events in the turnover of senescent erythrocytes, which alters our current understanding of how erythrocyte degradation is regulated. Disclosures No relevant conflicts of interest to declare.

PECULIARITIES OF CENTRAL HEMODYNAMICS AND PARAMETERS OF ERYTHROCYTES UNDER EXPOSURE TO EXTREME PROFESSIONAL FACTORS

The aim: to study the peculiarities of central hemodynamics and erythrocyte parameters under the influence of extreme occupational factors in firefighters with different lifetimes in the Federal Fire Service (FPS) of the Ministry of Emergency Measures for the Tver Region. Methods: 240 firefighters (age 25-47 years) were divided into three groups depending on the length of service: 1-6, 7-15, 16-25 years. Parameters of central hemodynamics were determined at the beginning of the working day shift according to the method of tetrapolar thoracic rheography. The absolute content of red blood cells in capillary blood was counted using a blood analyzer. Special techniques were used to determine deformability of their membrane. Results: most hemodynamic parameters deviated from the statutory values in the first group in comparison with other groups. This was regarded as an imbalance between the volume-time indeces of the blood circulation and the organism's needs under conditions of extreme occupational stress. Gradual formation of an adequate hemodynamic profile was detected with an increase in the length of service. This allows us to conclude about the mobile and reactive nature of hemodynamic changes in the body. Expressed hematologic changes, manifested in a decrease in the erythrocyte membrane deformability and increase in its rigidity, were found in the third group. The observed patterns at the last stage of the service probably reflect the conservative nature of negative shifts development. Conclusion: comparison of the dynamics of physiological changes in firefighters-rescuers of three groups with different service life in the Ministry of Emergency Measures revealed the reactive nature of hemodynamic changes and the conservative nature of hematological manifestations.

Measurements of three-dimensional refractive index tomography and membrane deformability of live erythrocytes from Pelophylax nigromaculatus

Unlike mammalian erythrocytes, amphibian erythrocytes have distinct morphological features including large cell sizes and the presence of nuclei. The sizes of the cytoplasm and nuclei of erythrocytes vary significantly over different species, their environments, or pathophysiology, which makes hematological studies important for investigating amphibian species. Here, we present a label-free three-dimensional optical quantification of individual amphibian erythrocytes from frogs Pelophylax nigromaculatus (Rana nigromaculata). Using optical diffraction tomography, we measured three-dimensional refractive index (RI) tomograms of the cells, which clearly distinguished the cytoplasm and nuclei of the erythrocytes. From the measured RI tomograms, we extracted the relevant biochemical parameters of the cells, including hemoglobin contents and hemoglobin concentrations. Furthermore, we measured dynamic membrane fluctuations and investigated the mechanical properties of the cell membrane. From the statistical and correlative analysis of these retrieved parameters, we investigated interspecific differences between frogs and previously studied mammals.

Influence of the course of treatment by injections of ozonized saline on rheological properties of erythrocytes in patients with complex pathology

With help of comprehensive methods of piezodynamic aggregometry in a microvolume and gradient ektacytometry the study was carried out to evaluate rheological properties of erythrocyte in patients with complex pathology before and after each injection of ozonated physiological solution. It was shown that after administration of physiological saline and after each session of ozone therapy occurs reduction of minimum aggregates strength and rate of spontaneous aggregation like and microviscosity and increase of deformability and water permeability of erythrocyte membranes. Dynamics of changes in the studied parameters of erythrocytes shows the improvement of the rheological properties of blood in patients not only immediately after the procedure, but and after update of blood in 2 weeks, 1 and 2 months after the course.

Erythrocyte oxidative stress is associated with cell deformability in patients with retinal vein occlusion

Background Retinal vein occlusion (RVO) is characterized by vision loss resulting from hypoperfusion and hypoxia of the retina. RVO pathogenesis is not yet fully understood, although blood hyperviscosity has been observed. Erythrocyte deformability plays a key role in determining blood viscosity, and it is critical to microvascular perfusion and oxygen delivery. It has been shown that oxidative stress-induced erythrocyte membrane fluidity alterations are linked to the progression of cardiovascular diseases. Objectives To determine whether erythrocytes from RVO patients show signs of oxidative stress, and whether this condition can modify the hemorheologic profile in these patients. Patients and Methods We analyzed the entire hemorheologic profile and erythrocyte oxidative stress - reactive oxygen species (ROS) production and membrane lipid peroxidation - in 128 RVO patients and 128 healthy subjects, matched for age and sex. Fluorescence anisotropy was used to evaluate the fluidity of erythrocyte membranes. Results In RVO patients, erythrocyte oxidative stress was present and positively correlated with whole blood viscosity and erythrocyte deformability. Multivariate linear regression analysis after adjustment for age, cardiovascular risk factors, medications, leukocyte number and mean corpuscular volume indicated that erythrocyte-derived ROS and erythrocyte lipid peroxidation were significantly and positively correlated with erythrocyte membrane viscosity and deformability. Moreover, in vitro experiments demonstrated that ROS have a key role in erythrocyte membrane fluidity. Conclusions Our findings indicate that erythrocyte oxidative stress plays a key role in the pathogenesis of RVO, and pave the way to new therapeutic interventions.

Optical assay of erythrocyte function in banked blood.

Stored red blood cells undergo numerous biochemical, structural, and functional changes, commonly referred to as storage lesion. How much these changes impede the ability of erythrocytes to perform their function and, as result, impact clinical outcomes in transfusion patients is unknown. In this study we investigate the effect of the storage on the erythrocyte membrane deformability and morphology. Using optical interferometry we imaged red blood cell (RBC) topography with nanometer sensitivity. Our time-lapse imaging quantifies membrane fluctuations at the nanometer scale, which in turn report on cell stiffness. This property directly impacts the cell's ability to transport oxygen in microvasculature. Interestingly, we found that cells which apparently maintain their normal shape (discocyte) throughout the storage period, stiffen progressively with storage time. By contrast, static parameters, such as mean cell hemoglobin content and morphology do not change during the same period. We propose that our method can be used as an effective assay for monitoring erythrocyte functionality during storage time.

Micrometric segregation of fluorescent membrane lipids: relevance for endogenous lipids and biogenesis in erythrocytes

Micrometric membrane lipid segregation is controversial. We addressed this issue in attached erythrocytes and found that fluorescent boron dipyrromethene (BODIPY) analogs of glycosphingolipids (GSLs) [glucosylceramide (BODIPY-GlcCer) and monosialotetrahexosylganglioside (GM1BODIPY)], sphingomyelin (BODIPY-SM), and phosphatidylcholine (BODIPY-PC inserted into the plasma membrane spontaneously gathered into distinct submicrometric domains. GM1BODIPY domains colocalized with endogenous GM1 labeled by cholera toxin. All BODIPY-lipid domains disappeared upon erythrocyte stretching, indicating control by membrane tension. Minor cholesterol depletion suppressed BODIPY-SM and BODIPY-PC but preserved BODIPY-GlcCer domains. Each type of domain exchanged constituents but assumed fixed positions, suggesting self-clustering and anchorage to spectrin. Domains showed differential association with 4.1R versus ankyrin complexes upon antibody patching. BODIPY-lipid domains also responded differentially to uncoupling at 4.1R complexes [protein kinase C (PKC) activation] and ankyrin complexes (in spherocytosis, a membrane fragility disease). These data point to micrometric compartmentation of polar BODIPY-lipids modulated by membrane tension, cholesterol, and differential association to the two nonredundant membrane:spectrin anchorage complexes. Micrometric compartmentation might play a role in erythrocyte membrane deformability and fragility.

Effect of Short-Term Hyperglycemia on Protein Kinase C Alpha Activation in Human Erythrocytes

Diabetes mellitus, characterized by chronic hyperglycemia, is known to have a deleterious effect on erythrocyte structure and hemodynamic characteristics, which eventually contribute to diabetes-associated vascular complications. Protein kinase C alpha (PKCα) is a major regulator of many metabolic processes and structural changes in erythrocytes, and may play a significant role in the development of hyperglycemia-mediated cellular abnormalities. We hypothesized that acute hyperglycemic stress may affect erythrocyte structure and metabolic properties through its effect on PKCα membrane content and activity. Erythrocytes, from healthy individuals acutely exposed to a glucose enriched media, showed a significant decrease in the membranous fraction of PKCα and its phosphorylation (p = 0.005 and p = 0.0004, respectively). These alterations correlated with decreased affinity of PKCα to its membrane substrates (4.1R and GLUT1) and reduced RBC deformability (p = 0.017). Pre-activation of erythrocytes with PKC activator, PMA, minimized the effect of glucose on the membrane PKCα fraction and RBC deformability (p > 0.05). Acute glycemia-induced inhibition of PKCα membranous translocation and activation is associated with reduced erythrocyte membrane deformability.

Hemorheological Effects of Valsartan in L-NAME Induced Hypertension in Rats

Animal models are a useful tool, for example, in the study of hypertension, but its use requires robust knowledge and well characterized models in order to extrapolate the obtained results. Nitric oxide is an important regulator of vascular function and blood pressure. The chronic administration of nitric oxide synthase (NOS) inhibitors provides an animal experimental model of hypertension. Our study aims to investigate the hemorheological effects of (i) N  -nitro-L-arginine methyl ester (L-NAME) added daily to Sprague-Dawley rats in drinking water and (ii) valsartan, an angiotensin II AT1-receptor antagonist, administration when the Sprague-Dawley rats acquired the hypertensive state. In three experimental groups (Control, Hypertensive and Valsartan) systolic blood pressure was measured and blood samples were collected for determination of erythrocyte membrane deformability and fluidity as well as blood and plasma viscosities. L-NAME intake induces an increase in the systolic blood pressure indicating the development of systemic hypertension. Concerning the hemorheological parameters, the erythrocyte deformability is decreased in the hypertensive animal group and on contrary the erythrocyte membrane fluidity increased being both parameters values reverted after valsartan administration. Valsartan also decreases the plasma and blood viscosities values obtained in the animal group which have acquired systemic hypertension after L-NAME intake. In conclusion, the angiotensin II AT1-receptor antagonist, valsartan, restores in hypertensive Sprague-Dawley rats L- NAME- dependent their systolic blood pressure to the physiological values, as well as, normalized their hemorheological parameters values; due to the similarity effects to human essential hypertension we conclude that this can be a suitable animal model for hemorheological studies in the field of hypertension.

Ligation of complement receptor 1 increases erythrocyte membrane deformability

AbstractMicrobes as well as immune complexes and other continuously generated inflammatory particles are efficiently removed from the human circulation by red blood cells (RBCs) through a process called immune-adherence clearance. During this process, RBCs use complement receptor 1 (CR1, CD35) to bind circulating complement-opsonized particles and transfer them to resident macrophages in the liver and spleen for removal. We here show that ligation of RBC CR1 by antibody and complement-opsonized particles induces a transient Ca++ influx that is proportional to the RBC CR1 levels and is inhibited by T1E3 pAb, a specific inhibitor of TRPC1 channels. The CR1-elicited RBC Ca++ influx is accompanied by an increase in RBC membrane deformability that positively correlates with the number of preexisting CR1 molecules on RBC membranes. Biochemically, ligation of RBC CR1 causes a significant increase in phosphorylation levels of β-spectrin that is inhibited by preincubation of RBCs with DMAT, a specific casein kinase II inhibitor. We hypothesize that the CR1-dependent increase in membrane deformability could be relevant for facilitating the transfer of CR1-bound particles from the RBCs to the hepatic and splenic phagocytes.

Diamide decreases deformability of rabbit erythrocytes and attenuates low oxygen tension-induced ATP release

Exposure of erythrocytes to reduced oxygen (O(2)) tension activates the heterotrimeric G-protein Gi, resulting in the accumulation of cyclic AMP (cAMP) and release of ATP. The mechanism by which exposure of erythrocytes to reduced O(2) tension activates Gi is not known. Here we investigate the hypothesis that, in rabbit erythrocytes, ATP release in response to exposure to reduced O(2) tension is linked to erythrocyte membrane deformability. If this hypothesis is correct, then decreasing the deformability of the erythrocyte membrane should decrease the release of ATP in response to reduced O(2) tension. We report that treating erythrocytes with diamide, a compound that decreases erythrocyte deformability, inhibits low O(2) tension-induced ATP release. Treating erythrocytes with diamide does not, however, interfere with cAMP accumulation or ATP release in response to a direct activator of Gi (mastoparan 7) or in response to receptor-mediated activation of Gs (the prostacyclin analog, iloprost). These results demonstrate that diamide (100 micromol/L) does not directly inhibit the signaling pathways for ATP release from rabbit erythrocytes and support the hypothesis that low O(2) tension-induced ATP release from these cells is linked to membrane deformability.

Fundamental laws of the deformational behavior of erythrocytes in shear flow

The dependences of the deformability parameter of erythrocytes on the shear stress in the Couette flow upon a change in their membrane rigidity or internal-content viscosity have been investigated by the diffractometric (ectacytometric) method. The results obtained suggest that the yield stress of cells measured by this method reflects the deformability of erythrocyte membranes, and the slope of the deformation curve rectified in the semilogarithmic coordinate system depends on the viscosity of the internal content of the cell. A parameter such as the limit deformation of erythrocytes is primarily determined by the viscosity of the membrane cytoskeleton.