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1.
The mechanical properties of sickle erythrocyte membranes were evaluated in the ektacytometer. When ghosts from the total red blood cell population were examined, the rigidity of the resealed ghosts and their rate of fragmentation by shear stress (t1/2) were normal. However, fractionation on Stractan density gradients revealed that sickle cells were heterogenous in their membrane mechanical properties. The ghosts from dense cell fractions exhibited both increased rigidity and decreased stability. Presumably, these altered mechanical properties are a reflection of the well-documented biochemical damage found in irreversibly sickle cell membranes. Nevertheless, neither of the alterations in mechanical properties are likely to be significant elements in the hemolysis of sickle cell anemia. Earlier studies of abnormal erythrocytes suggest that increases in membrane rigidity per se do not increase hemolysis, and they are, therefore, unlikely to do so in this case. The stability of membranes from the dense cell fractions was reduced to about two thirds of the control value. Comparison with the results of studies of red blood cell membranes with genetically defective or deficient spectrin suggests that a reduction in t 1/2 of 50% is not associated with significant increases in the rate of hemolysis. Although altered ghost stability and flexibility can be demonstrated in dense sickle cells, these changes in membrane mechanical properties are not likely to be significant factors in the hemolytic process. 相似文献
2.
Oxidation-induced changes in microrheologic properties of the red blood cell membrane 总被引:7,自引:2,他引:5
It has been hypothesized that some of the irreversible microrheologic abnormalities of sickle red blood cell (RBC) membranes could result from autoxidative perturbation. To model this possibility, we used micromechanical manipulation to examine the static extensional rigidity and inelastic or plastic behavior of normal RBCs exposed to phenazine methosulfate (PMS), an agent that generates superoxide from within the cell. In response to this stress, RBC membranes became stiff as evidenced by increasing extensional rigidity. At 50 mumol/L PMS they were as stiff as the membranes of most dense, dehydrated sickle RBCs; and at 25 mumols/L PMS the membranes were similar to somewhat less dense sickle RBCs. When examined for inelastic behavior, RBCs exposed to PMS even at 10 mumols/L showed hysteresis in loading and unloading phases of the curve relating aspiration length to suction pressure, and they developed membrane bumps that persisted after RBC release from the pipette. Examination of single cells in both isotonic and hypotonic buffers showed that the effect of PMS on RBC microheology is not mediated by cellular dehydration. Independent confirmation of the membrane stiffening effect of PMS was obtained by ektacytometric analysis of resealed RBC ghosts, with sickle-like increases in membrane rigidity observed between 50 and 100 mumol/L PMS. The rigidity of these ghosts was partially ameliorated by exposure to a thiol reductant. In terms of biochemical abnormalities, treated RBCs became significantly different from control RBCs at 25 mumol/L PMS, at which point they just began to enter the sickle range for amounts of membrane thiol oxidation and membrane-associated heme. The sickle average was achieved at 50 mumol/L PMS (for thiol oxidation) to 100 mumol/L PMS (for membrane heme). Thus, micromolar concentrations of PMS induce abnormalities of membrane microrheology that closely mimic those of unmanipulated sickle RBCs while reproducing similar degrees of oxidative biochemical change. We conclude that membrane protein oxidation could explain existence of an irreversible component to the abnormal rheology of the sickle membrane. 相似文献
3.
Huang Z Louderback JG King SB Ballas SK Kim-Shapiro DB 《American journal of hematology》2001,67(3):151-156
Hydroxyurea is a drug that is used to treat some patients with sickle cell disease. We have measured the deformability of sickle erythrocytes incubated in hydroxyurea in vitro and found that hydroxyurea acts to decrease the deformability of these cells. The deformability of normal erythrocytes was not significantly affected by hydroxyurea except at very high concentrations. Hydroxyurea also did not consistently reduce the deformability of sickle erythrocyte ghosts. We propose that the decreased deformability, observed in vitro, is due to the formation of methemoglobin and other oxidative processes resulting from the reaction of hydroxyurea and oxyhemoglobin. Although the reaction with normal hemoglobin is similar to that of sickle hemoglobin, the sickle erythrocytes are affected more. We propose that the sickle erythrocyte membrane is more susceptible to the reaction products of the reaction of hemoglobin and hydroxyurea. An earlier report has shown that hydroxyurea increases the deformability of erythrocytes in patients on hydroxyurea. Taken together, these data suggest that the improved rheological properties of sickle erythrocytes in vivo are due to the elevated numbers of F cells [cells with fetal hemoglobin]. The presence of the nitrosyl hemoglobin or methemoglobin from the reaction with hydroxyurea may also benefit patients in vivo by reducing sickling. 相似文献
4.
Deformability of normal and sickle erythrocytes was measured by means of micropipette elastimetry with determination of intrinsic membrane rigidity (P) and total cell deformability (Pt). In the elastimetric technique employed, negative pressure at the pipette tip was generated and measured continuously. Membrane rigidity is defined as the negative pressure, in mm H2O, required to induce a hemispherical projection of the cell surface into the micropipette, and total cell deformability as the negative pressure required to aspirate the entire cell into the pipette lumen. Membrane rigidity for oxygenated sickle discocytes was not statistically different from that of control normal discocytes, but Pt measurements were significantly higher for sickle than normal discocytes. Irreversibly sickled cells (ISCs) had markedly increased membrane rigidity and whole cell deformability when compared to control normal cells. Mildly deformed ISCs and severely deformed ISCs at ambient pO2, both showed significantly higher mean membrane rigidity values than sickle discocytes and reversibly sickled cells. Sickle and normal discocytes both showed membrane elasticity with reversion to original cell shape following release of the cell from its aspirated position at the pipette tip. ISCs, however, exhibited elastic deformation of the membrane. These studies provide further evidence of progressive alteration of the sickle cell membrane induced by the sickling-unsickling process, culminating in formation of the ISC, and suggest a role for the ISC membrane abnormality in the pathologic rheology of sickle cell disease. 相似文献
5.
A hybrid erythrocyte model for membrane studies in sickle cell disease has been developed. The model consists of normal red cell membranes containing hemoglobin S and sickle cell membranes containing hemoglobin A. In hybrids, complete hemoglobin exchange has been achieved together with restoration of low membrane permeability to potassium. Normal membranes containing HbS sickle upon deoxygenation and assume the characteristic appearance of irreversibly sickled cells (ISC) after prolonged anoxia. It is suggested that the hybrid model will be useful in defining further the process of ISC formation and in studying the influence of sickle hemoglobin upon the function of the surrounding membrane. 相似文献
6.
Little data exist for the mechanical properties of individual irreversible or reversible sickle cells (ISC and RSC, respectively), nor is the process of ISC formation well understood. For oxygenated ISC and density-fractionated RSC, we have used micropipette techniques to measure cell surface area (SA) and volume (V), membrane shear elastic modulus (mu), time constant for viscoelastic shape recovery (tc), and hence to calculate membrane surface viscosity (eta = mu X tc). Volume loss associated with increasing cell density was accompanied by a proportionately smaller surface area decrease; SA/V ratio thus increased for denser cells, with ISC having the highest values. Membrane area loss by fragmentation must thus be accompanied by an accelerated decrease in cell volume. ISC had relatively rigid membranes (mu 130% above normal controls) and tc close to normal values, so that their effective membrane viscosity was more than double control. RSC had viscoelastic properties close to control, but showed wider variation between sickle cell donors and within samples. Measurements on density-separated RSC showed that, on average, mu was nearly constant, but that tc was longer for the densest cells, with their eta approaching ISC levels. A small subpopulation of RSC were found that had mu close to ISC values. Hypotonically swollen ISC (with internal hemoglobin concentration decreased to normal levels) retained their increased membrane stiffness but had markedly decreased tc, so that their eta approached normal values. The results show that elevated hemoglobin concentration influences the viscoelastic behavior of ISC and RSC, but that an irreversible change in membrane elasticity also occurs for ISC. These data suggest that ISC formation occurs via a two- stage process: (1) accelerated volume loss leading to increased cytoplasmic and effective membrane viscosity; (2) a sharp rise in membrane rigidity, presumably linked to membrane structural alteration. 相似文献
7.
Previously we demonstrated that sickle erythrocytes sedimenting at high densities after gradient centrifugation contain higher levels of surface immunoglobulin bound in vivo in comparison to low-density erythrocytes from the same patient. The present study examines the possibility that binding of autologous IgG to sickle erythrocytes may be associated with the sickling phenomenon. In the present study we subjected low-density erythrocytes to prolonged sickling under nitrogen in the presence of platelet-poor autologous plasma with added glucose for 24 hours (37 degrees C). After reoxygenation IgG bound in vitro was quantified by a nonequilibrium 125iodinated protein A-binding assay and by flow cytometry. Results show that sickle erythrocytes incubated under nitrogen bound significantly (P less than .001) more IgG, 439 +/- 41, molecules of IgG per cell (mean +/- SD) compared with sickle cells incubated under oxygenation (227 +/- 12 molecules of IgG per red cell) or compared with 196 +/- 26 molecules IgG per cell for untreated sickle cells. In contrast, normal erythrocytes incubated in autologous plasma exhibited no detectable IgG binding in vitro under either oxygenation or deoxygenation. Flow cytometry shows that deoxygenation of sickle cells generated a two-to-sixfold increase in the subpopulation of brightly fluorescent IgG-positive cells in comparison to oxygenated sickle cells and a 13.5% +/- 3.1% (mean +/- SD) increase in median fluorescence intensity for fluorescein isothiocyanate-labeled deoxygenated sickled cells compared with labeled oxygenated sickle cells. Our studies demonstrate that prolonged sickling will induce in vitro binding of autologous IgG to sickle erythrocytes. These findings indicate that sickle erythrocytes may be unique when compared with erythrocytes from other nonimmunologic hemolytic anemias or senescent red cells in that the primary events producing surface antigens recognized by autoantibody may include the sickling process. These findings also suggest that sickling in vivo may generate membrane alterations in sickle erythrocytes that lead to cumulative binding of autoantibody in vivo. 相似文献
8.
Abnormal deposition of hemichrome on the inner aspect of the sickle red cell membrane promotes premature cell demise. The steps proximate to hemichrome formation in these cells are poorly understood. To test the hypothesis that the pathologic deposits of free ferric iron located on the inner aspect of sickle cell membranes would be redox active and promote oxidation of soluble oxyhemoglobin, we incubated native versus iron-stripped sickle or normal ghost membranes with oxyhemoglobin S. We found that sickle membranes exerted an exaggerated effect on methemoglobin formation in solution, an effect completely accounted for by their abnormal content of free iron. This ability of sickle membranes to promote hemoglobin oxidation was not diminished by catalase or by presence of a high-affinity, iron-inactivating chelator that is unable to remove membrane iron. Examination of those membranes likewise revealed that their free iron content promoted deposition of additional heme-protein. These results establish that the potential redox couple formed by membrane-associated ferric iron and cytoplasmic oxyhemoglobin is promotive of hemoglobin oxidation and deposition of hemichrome on the membrane. This predicts that removal of pathologic membrane iron might help prevent the detrimental formation of methemoglobin and hemichrome in vivo, insofar as this is accelerated by transition metal. 相似文献
9.
To assess the role of intracellular hemoglobin concentration in the deformability of sickle (HbSS) cells after deoxygenation, rheologic coefficients (static rigidity E and dynamic rigidity eta) of density- fractionated individual sickle erythrocytes (SS cells) were determined as a function of oxygen tension (pO2) using the micropipette technique in a newly developed experimental chamber. With stepwise deoxygenation, E and eta values showed no significant increase before morphologic sickling but rose sharply after sickling. In denser cells, continued deoxygenation led to steep rises of E and eta toward infinity, as the cell behaved as a solid. The pO2 levels at which rheologic and morphologic changes occurred for individual SS cells during deoxygenation varied directly with the cell density. The extent of recovery in E and eta during reoxygenation varied inversely with the cell density. These results provide direct evidence that the intracellular sickle hemoglobin (HbS) concentration of SS cells plays an important role in their rheologic heterogeneity in deoxygenation and reoxygenation. The elevations of eta during pO2 alteration were greater than those of E, especially for the denser cells, suggesting the importance of the elevated dynamic rigidity in initiating microcirculatory disturbances in sickle cell disease. 相似文献
10.
Nonrandom association of free iron with membranes of sickle and beta- thalassemic erythrocytes 总被引:2,自引:2,他引:2
Repka T; Shalev O; Reddy R; Yuan J; Abrahamov A; Rachmilewitz EA; Low PS; Hebbel RP 《Blood》1993,82(10):3204-3210
To further define the nature of abnormal iron deposits on the membranes of pathologic red blood cells, we have used sickle cell anemia (HbSS), HbSC, and beta-thalassemic erythrocytes (RBCs) to prepare inside-out membranes (IOM) and insoluble membrane aggregates (AGGs) containing coclustered hemichrome and band 3. Study of IOM from HbSC and thalassemic patients showed that amounts of heme iron and, especially, free iron were much higher in patients who had undergone surgical splenectomy. The membrane AGGs from HbSS and beta-thalassemic RBCs contained much more globin than heme, with this discrepancy being variable from patient to patient. Although these AGGs were enriched (compared with the ghosts from which they were derived) for heme, as expected, less than 10% of total ghost heme was recovered in them. Remarkably, these AGGs also were enriched for nonheme iron, markedly so in some patients. Iron binding studies showed that the association of free iron with these hemichrome/band 3 AGGs is explained by the fact that free iron binds to denatured hemoglobin. These results document that free iron is nonrandomly associated with the membranes of sickle and beta-thalassemic RBCs. Whether this plays a causative role in the premature removal of such cells from the circulation remains to be seen. 相似文献
11.
Cytosolic free calcium levels in sickle red blood cells 总被引:6,自引:0,他引:6
In this study, we used a recently developed nuclear magnetic resonance (NMR) technique to measure ionized calcium in sickle erythrocytes. The NMR technique, which involves 19F NMR studies of a fluorinated calcium chelator quinMF, [2-(2-amino-4-methyl-5-fluorophenoxy)methyl-8- aminoquinoline-N,N,N',N'- tetraacetic acid] provides a novel approach to the study of ionized calcium in erythrocytes since the presence of hemoglobin precludes the use of fluorescent calcium indicators. The mean value for ionized calcium in oxygenated sickle erythrocytes was 18 +/- 2 nmol/L (SE). Experiments with normal RBCs gave a mean value of 21 +/- 2 nmol/L (SE). After 1 hour of deoxygenation, mean values for ionized calcium in sickle erythrocytes did not increase as compared with values obtained under oxygen. To investigate whether deoxygenation stimulated endocytosis, sickle erythrocytes were deoxygenated for 1 hour in the presence of impermeant FBAPTA (1,2 bis-(2-amino-5- fluorophenoxy) ethane N,N,N',N'-tetraacetic acid). Cells were then separated from the extracellular medium and assayed for the presence of FBAPTA; they had incorporated significant quantities of the extracellular FBAPTA. This incorporation was not observed with normal erythrocytes. These data are consistent with at least a portion of the elevation in total cell calcium in sickle erythrocytes arising as a consequence of an endocytotic process in which extracellular calcium ions are incorporated into vesicles. Additional experiments show that these intracellular vesicles accumulate Ca2+ on further deoxygenation, consistent with a transient increase in ionized cell calcium. These studies represent the first use of NMR spectroscopy to evaluate endocytotic processes. 相似文献
12.
A U Orjih R Chevli C D Fitch 《The American journal of tropical medicine and hygiene》1985,34(2):223-227
In an effort to elucidate a mechanism of genetic resistance to malaria, we asked whether a toxic form of heme is included in the excess of ferriprotoporphyrin IX (FP) which has been reported to accumulate as hemichromes in sickle cells. When FP is bound to certain erythrocytic elements, such as native hemoglobin, it is inaccessible to bind chloroquine with high affinity and is nontoxic. However, when FP is accessible to bind chloroquine with high affinity, it has been demonstrated to be sufficiently free to have membrane toxicity and, under certain conditions, to lyse Plasmodium falciparum parasites. [14C]-chloroquine was used, therefore, as a reporter molecule to evaluate the quantity, accessibility, and potential toxicity of FP released from hemoglobin. Intact erythrocytes from subjects with sickle cell anemia bound approximately 71 mumoles of chloroquine per kg with an apparent Kd of 10(-6) M. Erythrocytes from normal subjects or subjects with sickle trait bound little or no chloroquine with high affinity. Since the oxidant stress introduced by malaria parasites would increase the tendency for denaturation of hemoglobin S with additional release of FP, we suggest that FP toxicity accounts for the death of malaria parasites in sickle cells. 相似文献
13.
The molecular species composition of phosphatidylcholine affects cellular properties in normal and sickle erythrocytes 总被引:1,自引:0,他引:1
The phosphatidylcholine specific transfer protein (PCTP) from bovine liver was used to retailor the molecular species composition of phosphatidylcholine (PC) in the membrane of normal (AA) and sickleable (SS) human erythrocytes. Changes in molecular species composition of PC altered morphology as well as cellular deformability and stability as measured with ektacytometry. In normal cells, replacement of native PC with 1-palmitoyl,2-arachidonoyl PC (PAPC) resulted in a decrease in osmotic fragility with no change in hydration, whereas replacement with 1,2-dipalmitoyl PC (DPPC) led to an increased osmotic fragility and cellular hydration. Replacement of native PC by 1-palmitoyl,2-oleoyl PC (POPC) in normal cells had no apparent effect on these parameters. In contrast, replacement of native PC in sickle cells with either PAPC, DPPC or POPC led to cellular hydration. Facilitation of PC exchange between subpopulations of SS cells separated on buoyant density also led to cellular hydration. These observations suggest that the state of hydration of sickle cells can be modified by the fatty acyl composition of PC and illustrate a a role for the lipid core in the observed permeability changes in sickle erythrocytes. They also raise the interesting possibility that the state of cellular hydration of sickle cells may be modulated by altering the molecular species composition of the membrane phospholipids. 相似文献
14.
The Interaction between (Ca2+ + Mg2+ )-ATPase and the Soluble Activator (Calmodulin) in Erythrocytes Containing Haemoglobin S 总被引:1,自引:0,他引:1
In normal erythrocytes, a membrane-bound (Ca2+ + Mg2+)-ATPase is stimulated by a soluble activator, calmodulin. Since cells containing Hb S accumulate excessive Ca2+, the defect could lie in either the (Ca2+ + Mg2+)-ATPase or calmodulin. To decide between these two possibilities, we prepared (Ca2+ + Mg2+)-ATPase from erythrocytes of normal (AA), sickle cell trait (AS) and sickle cell disease (SS) individuals. Calmodulin was prepared from haemolysates from AA and SS erythrocytes. The enzyme prepared from SS ghosts had lower specific activity than that from AA membranes. Furthermore, calmodulin from either source did not stimulate the ATPase of SS erythrocytes. Enzyme from AS cells had specific activity similar to that of enzyme prepared from SS membranes. The enzymatic activity of a mixed cell population obtained from an SS patient 8 d following exchange-transfusion was proportional to the per cent Hb A. These results indicate that calmodulin is unable to interact with the enzyme site on the SS membrane. This inability is believed to be due to a specific property of the membrane and not an abnormality of calmodulin itself. 相似文献
15.
Nonheme iron in sickle erythrocyte membranes: association with phospholipids and potential role in lipid peroxidation 总被引:5,自引:0,他引:5
Previous studies documented the abnormal association of heme and heme proteins with the sickle RBC membrane. We have now examined RBC ghosts and inside-out membranes (IOM) for the presence of nonheme iron as detected by its formation of a colored complex with ferrozine. Sickle ghosts have 33.8 +/- 18.2 nmol nonheme iron/mg membrane protein, and sickle IOM have 4.3 +/- 3.0 nmol/mg. In contrast, normal RBC ghosts and IOM have no detectable nonheme iron. The combination of heme and nonheme iron in sickle IOM averages nine times the amount of membrane- associated iron in normal IOM. Kinetics of the ferrozine reaction show that some of this nonheme iron on IOM reacts slowly and is probably in the form of ferritin, but most (72% +/- 18%) reacts rapidly and is in the form of some other biologic chelate. The latter iron compartment is removed by deferoxamine and by treatment of IOM with phospholipase D, which suggests that it represents an abnormal association of iron with polar head groups of aminophospholipids. The biologic feasibility of such a chelate was demonstrated by using an admixture of iron with model liposomes. Even in the presence of tenfold excess adenosine diphosphate, iron partitions readily into phosphatidylserine liposomes; there is no detectable association with phosphatidylcholine liposomes. To examine the bioavailability of membrane iron, we admixed membranes and t-butylhydroperoxide and found that sickle membranes show a tenfold greater peroxidation response than do normal membranes. This is not due simply to a deficiency of vitamin E, and this is profoundly inhibited by deferoxamine. Thus, while thiol oxidation in sickle membranes previously was shown to correlate with heme iron, the present data suggest that lipid peroxidation is related to nonheme iron. In control studies, we did not find this pathologic association of nonferritin, nonheme iron with IOM prepared from sickle trait, high-reticulocyte, postsplenectomy, or iron-overloaded individuals. These data provide additional support for the concept that iron decompartmentalization is a characteristic of sickle RBCs. 相似文献
16.
The sickle hemoglobin (HbS)-containing erythrocyte and its membrane represent a logical target for sickle cell disease therapy. Several antisickling agents which interfere with HbS polymerization have been studied over the last 30 years, but none has overcome the challenge of delivering high concentrations inside the sickle red blood cell without toxicity. The sickle erythrocyte membrane has also been targeted for therapeutic developments. Prevention of sickle cell dehydration by use of specific blockers of ion transport pathways mediating potassium loss from the sickle erythrocyte has been shown to be a feasible strategy in vitro, in vivo in transgenic sickle mice, and in patients. Other approaches have focused on improving the hemorheology of sickle erythrocytes and reducing their abnormal adhesion to endothelial cells. These potential treatments could be used alone or in combination with other approved therapies, such as hydroxyurea. 相似文献
17.
H Mizukami D E Bartnicki S Burke G J Brewer I F Mizukami 《American journal of hematology》1986,21(3):233-241
The birefringence formation of sickle cell hemoglobin (HbS) in a thin liquid layer was observed while its environment was deoxygenated at different rates, and the effect of membrane was examined. Under slow rate of deoxygenation at 37 degrees C, at pH 7.4, the birefringence of purified HbS appeared at a concentration higher than 24% and its relative magnitude increased as the concentration was increased. Similarly, the partial pressure of oxygen, at which the birefringence formation was evident, increased from 0 to 27 torr as the concentration of HbS was increased from 24 to 28%, but it remained the same above this protein concentration. In all the samples tested relative birefringence was largest at the slow rate of deoxygenation (30 torrO2/min) and the magnitude decreased as the rate of deoxygenation was increased. The samples showed different sensitivity to the rate of deoxygenation. For example, while the total untreated hemolysate made by freeze-thawing of packed sickle cells was most resistant to the increased rates of deoxygenation, purified HbS was not. Washed open ghosts partially restored the birefringence formation pattern of purified HbS. The results indicate that the inner surface of the membranes of erythrocytes could behave as a template for large HbS polymer formation at relatively higher rates of deoxygenation. 相似文献
18.
Sickle erythrocyte (RBC) membranes were previously shown to manifest increased Fenton activity (iron-dependent, peroxide-driven formation of hydroxyl radical [.OH]) compared with normal RBC membranes, but the nature of the catalytic iron was not defined. We now find that sickle membranes exposed to superoxide (.O2-) and hydrogen peroxide (H2O2) have three distinct iron compartments able to act as Fenton catalysts: preexisting free iron, free iron released during oxidant stress, and a component that cannot be chelated with deferoxamine (DF). In a model system, addition of iron compounds to normal ghosts showed that free heme, hemoglobin, Fe/adenosine diphosphate (ADP), and ferritin all catalyze .OH production; concurrent inhibition studies using DF documented that the unchelatable Fenton component is free heme or hemoglobin. During exposure to peroxide only, the iron in sickle membranes was unable to act as a Fenton catalyst without addition of a reducing agent. At physiologic concentrations, both ascorbate and glutathione restored Fenton activity. Lipid peroxidation studies showed that at physiologic levels ascorbate acts primarily as an antioxidant; however, as pharmacologic levels are reached, its pro-oxidant effects predominate. This study elucidates the catalytic ability of the iron compartments in the sickle cell membrane, the importance of which relates to the potential role of .OH in membrane damage. It also illustrates the potential participation of cytoplasmic reducing agents in this process, which may be especially relevant in the context of administration of supraphysiologic doses of ascorbate to sickle cell patients. 相似文献
19.
1. By transfusing sickle cell anemia erythrocytes with a relatively high concentration of F hemoglobin into normal recipients, it was demonstrated that thedisappearance rates of the transfused cells and of their alkali resistant pigmentconsistently showed great discrepancies. These observations suggest an unequaldistribution of the F pigment within the erythrocyte population. A nonuniformdistribution of F hemoglobin could also be detected in vitro by exposing sicklecell anemia bloods to mechanical trauma for a longer period of time. The cellsmost resistant to trauma contained a higher percentage of F hemoglobin thanthe original blood specimen.2. The red cell population of patients with sickle cell anemia seems to be composed of three main fractions: (1) cells containing S hemoglobin and no or littleF hemoglobin, (2) cells containing both pigments and (3) cells containing Fpigment with no or little S hemoglobin.3. The erythrocytes carrying mostly S hemoglobin have the shortest life span,whereas the red cells containing mostly F hemoglobin have the longest survivaltime.4. The significance of these findings in regard to clinical and genetic aspectsof sickle cell anemia is discussed. No direct correlation is demonstrable in anindividual patient between the absolute amounts of either type S or type Fhemoglobin and the severity of the anemia. The latter depends on the variablesize of the portion of red cells containing mostly S hemoglobin, and also on theability of the marrow to replace this particular fraction. Submitted on August 5, 1952 Accepted on September 10, 1952 相似文献
20.
C A Reindorf J Kurantsin-Mills J B Allotey O Castro 《American journal of hematology》1985,19(3):229-236
The effects of oxygenated perfluorotributylamine (Fluosol-43) on the rheological properties of sickle (HbSS) erythrocytes have been determined by means of microviscometry and positive pressure cell filtration. Incubation of deoxygenated sickled erythrocytes (pO2 congruent to 30 mmHg) with oxygenated Fluosol-43 reduced the percentage of sickled erythrocytes from about 63 to 33%. Deoxygenation of 40% suspension of sickle erythrocytes in autologous plasma increased the viscosity by about 160% at shear rate of 1.15 sec-1. Incubation of the deoxygenated sickled erythrocytes with oxygenated Fluosol-43 significantly reduced the viscosity at the low shear rates. Filtration of 0.2% suspension of deoxygenated sickle erythrocytes through capillary-sized Nuclepore filters showed high resistance at low flow rates. Oxygenated Fluosol-43 increased the deformability of HbSS erythrocytes and thereby reduced the resistance at flow rates less than 1 ml/min. These data suggest that perfluorocarbons may be useful in reducing the propensity of hemoglobin S polymerization and sickling and thereby prevent tissue infarction in vaso-occlusive crisis. Therefore, the concept of examining the potential application of perfluorochemicals for alleviating severe vaso-occlusive events may be useful. 相似文献